Autoregulation

Distribution by Scientific Domains

Kinds of Autoregulation

  • blood flow autoregulation
  • cerebral autoregulation
  • flow autoregulation


  • Selected Abstracts


    Nitric oxide, superoxide and renal blood flow autoregulation in SHR after perinatal L -arginine and antioxidants

    ACTA PHYSIOLOGICA, Issue 4 2007
    M. P. Koeners
    Abstract Aim:, Nitric oxide (NO) and superoxide are considered to be regulatory in renal blood flow (RBF) autoregulation, and hence may contribute to development of hypertension. To extend our previous observations that dynamic NO release is impaired in the spontaneously hypertensive rat (SHR) we investigated, firstly, if superoxide dependency of RBF autoregulation is increased in SHR and, secondly, if the beneficial effect of perinatal supplementation in SHR is partly as a result of early correction of RBF autoregulation. We hypothesized that perinatal supplementation by restoring dynamic NO release and/or decreasing superoxide dependency and would improve life-long blood pressure regulation. Methods:, Autoregulation was studied using stepwise reductions in renal perfusion pressure in anaesthetized male SHR, SHR perinatally supplemented with arginine and antioxidants (SHRsuppl) and Wistar-Kyoto (WKY), prior to and during i.v. N, -nitro- l -arginine (NO synthase inhibitor) or tempol (superoxide dismutase mimetic). Results:, Spontaneously hypertensive rat displayed a wider operating range of RBF autoregulation as compared with WKY (59 4 vs. 33 2 mmHg, respectively; P < 0.01). Perinatal supplementation in SHR decreased mean arterial pressure, renal vascular resistance and the operating range of RBF autoregulation (43 3 mmHg; P < 0.01). In addition autoregulation efficiency decreased. RBF autoregulation characteristics shifted towards those of normotensive WKY. However, dynamic NO release was still impaired and no clear differences in superoxide dependency in RBF autoregulation between groups was observed. Conclusion:, Perinatal supplements shifted RBF autoregulation characteristics of SHR towards WKY, although capacity of the SHRsuppl kidney to modulate NO production to shear stress still seems impaired. The less strictly controlled RBF as observed in perinatally supplemented SHR could result in an improved long-term blood pressure control. This might partly underlie the beneficial effects of perinatal supplementation. [source]


    Autoregulation might explain why blood pressure is not associated with haematoma enlargement in acute intracerebral haemorrhage

    EUROPEAN JOURNAL OF NEUROLOGY, Issue 10 2008
    S. Sacco
    No abstract is available for this article. [source]


    Autoregulation of the HAC1 gene is required for sustained activation of the yeast unfolded protein response

    GENES TO CELLS, Issue 2 2004
    Naoki Ogawa
    Eukaryotic cells respond to the accumulation of unfolded proteins in the endoplasmic reticulum (ER) by activating a transcriptional induction program termed the unfolded protein response (UPR). The transcription factor Hac1p responsible for the UPR in Saccharomyces cerevisiae is tightly regulated by a post-transcriptional mechanism. HAC1 mRNA must be spliced in response to ER stress to produce Hac1p, which then activates transcription via direct binding to the cis -acting UPR element (UPRE) present in the promoter regions of its target genes. Here, we show that the HAC1 promoter itself responds to ER stress to induce transcription of its downstream gene, similarly to the KAR2 promoter; the KAR2 gene represents a major target of the UPR. Consistent with this observation, the HAC1 promoter contains an UPRE-like sequence, which is necessary and sufficient for the induction and to which Hac1p binds directly. Cells expressing the HAC1 gene from a mutant HAC1 promoter lacking the HAC1 UPRE could not maintain high levels of either unspliced or spliced HAC1 mRNA and became sensitive to ER stress when insulted for hours. Based on these results, we concluded that autoregulation of the HAC1 genes is required for sustained activation of the UPR and sustained resistance to ER stress. [source]


    Phosphorus and the regulation of nodulation in the actinorhizal symbiosis between Discaria trinervis (Rhamnaceae) and Frankia BCU110501

    NEW PHYTOLOGIST, Issue 1 2002
    Claudio Valverde
    Summary ,,After nitrogen (N), phosphorus (P) is the nutrient that most limits plant productivity. The role of P on growth and root nodulation was studied in the actinorhizal symbiosis between Discaria trinervis and Frankia, an intercellular infected N2,fixing association. ,,Growth, nodulation and nutrient content (N and P) were analysed in symbiotic plants receiving different supplies of P in nutrient solutions. The relative requirement of P for nodulation was analysed in P-deficient plants. ,,Nodule initiation was less impaired than general plant growth by low P. However, low P impaired nodule growth to a greater extent than plant growth. The proportion of nodule biomass, although not the number of nodules per plant, was stimulated by P supply. Autoregulation of nodulation was not affected by P. Use of N was limited by availability of P. Reserves of P in seeds were enough for the seedling to establish nodules. However nodule (and plant) growth was limited in the absence of exogenous P. ,,It is possible that P interacts with the feedback control of nodule growth that is associated with the plant demand for N. Leaf N : P ratio is negatively correlated with the proportion of nodule tissue. [source]


    Autoregulation of the cerebral circulation during sleep in newborn lambs

    THE JOURNAL OF PHYSIOLOGY, Issue 3 2005
    Daniel A. Grant
    Autoregulation is a vital protective mechanism that maintains stable cerebral blood flow as cerebral perfusion pressure changes. We contrasted cerebral autoregulation across sleep,wake states, as little is known about its effectiveness during sleep. Newborn lambs (n= 9) were instrumented to measure cerebral blood flow (flow probe on the superior sagittal sinus) and cerebral perfusion pressure, then studied during active sleep (AS), quiet sleep (QS) and quiet wakefulness (QW). We generated cerebral autoregulation curves by inflating an occluder cuff around the brachiocephalic artery thereby lowering cerebral perfusion pressure. Baseline cerebral blood flow was higher (P < 0.05) and cerebral vascular resistance lower (P < 0.05) in AS than in QW (76 8% and 133 15%, respectively, of the AS value, mean s.d.) and in QS (66 11% and 158 30%). The autoregulation curve in AS differed from that in QS and QW in three key respects: firstly, the plateau was elevated relative to QS and QW (P < 0.05); secondly, the lower limit of the curve (breakpoint) was higher (P < 0.05) in AS (50 mmHg) than QS (45 mmHg); and thirdly, the slope of the descending limb below the breakpoint was greater (P < 0.05) in AS than QS (56% of AS) or QW (56% of AS). Although autoregulation functions in AS, the higher breakpoint and greater slope of the descending limb may place the brain at risk for vascular compromise should hypotension occur. [source]


    Autoregulation in the choroid

    ACTA OPHTHALMOLOGICA, Issue 2009
    S ORGUL
    Purpose To compare subfoveal choroidal blood flow (ChBF) in sitting and supine position in normal volunteers. Methods ChBF was measured with laser Doppler flowmetry in 22 healthy volunteers (mean age SD: 24 5 years). Six independent measurements of choroidal blood flow were obtained in one randomly selected eye of each subject. Subsequently, the subjects assumed a supine position for 30 minutes and a new series of 6 measurements was obtained. Parallel hereto, systemic blood pressure and intraocular pressure were measured. Ocular perfusion pressure (OPP) was calculated based on formulas derived from ophthalmodynamometric studies. The influence of changing OPP on the change in ChBF was assessed in a linear regression analysis. Results The coefficient of variation for ChBF was 10.28% and 9.58% in the sitting and the supine position respectively. ChBF decreased by 6.6% (p=0.0017) in the supine position. The estimate for ophthalmic blood pressure in the supine position was adjusted to obtain a result of no change in OPP for no change in ChBF, yielding an average decrease for the estimate of OPP of 6.7% (p=0.0002). Change in OPP correlated significantly with change in ChBF (R2: 0.20; p=0.036) with a slope for the regression line of 1.04. Conclusion The comparable degree of change in ChBF and OPP and the linear relationship between the two parameters suggest a passive response of the choroidal circulation to the posture change. In contrast, the OPP estimates suggest a marked buffering of the change in perfusion pressure by the carotid system, compatible with a close control of the gradient in perfusion pressure between the heart and its branches within the carotid system. [source]


    Ocular blood flow autoregulation and the clinical implications of its alteration

    ACTA OPHTHALMOLOGICA, Issue 2009
    G GARHOFER
    Autoregulation is commonly defined as the ability of a vascular bed to adapt blood flow to changes in ocular perfusion pressure (pressure autoregulation) or to adapt to changes in metabolic need (metabolic autoregulation). Considering the high metabolic turnover of the eye, its intact function is strongly dependent on a stable blood supply, assured by an intact vascular autoregulation. However, it has been shown that in the recent years that several ocular diseases such as glaucoma, diabetic retinopathy or age related macula degeneration are associated with an impaired autoregulation. This vascular dysregulation may lead to an under- or overperfusion of the tissue and in turn to ischemia and/or oxidative stress. This talk seeks to summarize our current knowledge of autoregulation in the ocular vascular beds. Furthermore, the possible reasons of impaired autoregulation and how this may relate to ocular pathologies will be discussed. [source]


    Nitric oxide, superoxide and renal blood flow autoregulation in SHR after perinatal L -arginine and antioxidants

    ACTA PHYSIOLOGICA, Issue 4 2007
    M. P. Koeners
    Abstract Aim:, Nitric oxide (NO) and superoxide are considered to be regulatory in renal blood flow (RBF) autoregulation, and hence may contribute to development of hypertension. To extend our previous observations that dynamic NO release is impaired in the spontaneously hypertensive rat (SHR) we investigated, firstly, if superoxide dependency of RBF autoregulation is increased in SHR and, secondly, if the beneficial effect of perinatal supplementation in SHR is partly as a result of early correction of RBF autoregulation. We hypothesized that perinatal supplementation by restoring dynamic NO release and/or decreasing superoxide dependency and would improve life-long blood pressure regulation. Methods:, Autoregulation was studied using stepwise reductions in renal perfusion pressure in anaesthetized male SHR, SHR perinatally supplemented with arginine and antioxidants (SHRsuppl) and Wistar-Kyoto (WKY), prior to and during i.v. N, -nitro- l -arginine (NO synthase inhibitor) or tempol (superoxide dismutase mimetic). Results:, Spontaneously hypertensive rat displayed a wider operating range of RBF autoregulation as compared with WKY (59 4 vs. 33 2 mmHg, respectively; P < 0.01). Perinatal supplementation in SHR decreased mean arterial pressure, renal vascular resistance and the operating range of RBF autoregulation (43 3 mmHg; P < 0.01). In addition autoregulation efficiency decreased. RBF autoregulation characteristics shifted towards those of normotensive WKY. However, dynamic NO release was still impaired and no clear differences in superoxide dependency in RBF autoregulation between groups was observed. Conclusion:, Perinatal supplements shifted RBF autoregulation characteristics of SHR towards WKY, although capacity of the SHRsuppl kidney to modulate NO production to shear stress still seems impaired. The less strictly controlled RBF as observed in perinatally supplemented SHR could result in an improved long-term blood pressure control. This might partly underlie the beneficial effects of perinatal supplementation. [source]


    Impairment of cerebral autoregulation in diabetic patients with cardiovascular autonomic neuropathy and orthostatic hypotension

    DIABETIC MEDICINE, Issue 2 2003
    B. N. Mankovsky
    Abstract Aims Impaired cerebrovascular reactivity and autoregulation has been previously reported in patients with diabetes mellitus. However, the contribution of cardiovascular diabetic autonomic neuropathy and orthostatic hypotension to the pathogenesis of such disturbances is not known. The purpose of this study was to evaluate cerebral blood flow velocity in response to standing in patients with diabetes and cardiovascular autonomic neuropathy with or without orthostatic hypotension. Methods We studied 27 patients with diabetes,eight had cardiovascular autonomic neuropathy and orthostatic hypotension (age 46.4 13.5 years, diabetes duration 25.0 11.0 years), seven had autonomic neuropathy without hypotension (age 47.3 12.7 years, diabetes duration 26.4 12.1 years), and 12 had no evidence of autonomic neuropathy (age 44.1 13.8 years, diabetes duration 17.1 10.2 years),and 12 control subjects (age 42.6 9.7 years). Flow velocity was recorded in the right middle cerebral artery using transcranial Doppler sonography in the supine position and after active standing. Results Cerebral flow velocity in the supine position was not different between the groups studied. Active standing resulted in a significant drop of mean and diastolic flow velocities in autonomic neuropathy patients with orthostatic hypotension, while there were no such changes in the other groups. The relative changes in mean flow velocity 1 min after standing up were ,22.7 16.25% in patients with neuropathy and orthostatic hypotension, +0.02 9.8% in those with neuropathy without hypotension, ,2.8 14.05% in patients without neuropathy, and ,9.2 15.1% in controls. Conclusions Patients with diabetes and cardiovascular autonomic neuropathy with orthostatic hypotension show instability in cerebral blood flow upon active standing, which suggests impaired cerebral autoregulation. [source]


    Potential role of thioredoxin in immune responses in intestinal lamina propria T,lymphocytes

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2005
    Bernd Sido
    Abstract Thioredoxin (TRX) is a ubiquitous oxidoreductase with strong co-cytokine, chemoattractant and anti-apoptotic activities. TRX expression was found to be particularly elevated in the intestinal mucosa, where its physiologic function is entirely unknown. Here, we demonstrate a high level of TRX expression in lamina propria T,cells (LP-T) as opposed to autologous peripheral blood T,lymphocytes (PB-T). Addition of recombinant human TRX (rhTRX) to PB-T enhances TRX gene expression. This autoregulation involves the calcineurin signaling pathway, as rhTRX antagonizes the cyclosporine,A (CsA)- and tacrolimus-mediated suppression of TRX gene expression. Similarly, rhTRX reverses the suppression of IL-2 mRNA production by CsA and enhances cytokine production preferentially in prestimulated cells. The differential TRX expression in LP-T versus PB-T may thus contribute to the high-level, CsA-resistant IL-2 production characteristic for CD2-stimulated LP-T. Inversely, inactivation of TRX in LP-T through inhibition of TRX reductase abolishes cytokine gene expression. TRX may play a key role in the specialized intestinal microenvironment in amplifying immediate immune responses of LP-T whenever appropriate costimulation of LP-T is provided. [source]


    Cerebral perfusion in the elderly with nocturnal blood pressure fall

    EUROPEAN JOURNAL OF NEUROLOGY, Issue 7 2007
    A. Siennicki-Lantz
    Cerebrovascular disease may be linked with vascular autoregulation in aging. The aim of this study was to examine relation between nocturnal blood pressure (BP) fall and cerebral blood flow (CBF) changes in elderly men. The prospective ,Men born in 1914' cohort study has been in progress since 1968 and included 809 subjects. After 14 years from the last follow up, 97 subjects reached the age of 82 and underwent CBF measurement and 24 h ambulatory blood pressure monitoring. Diastolic BP at night decreased in 84 subjects with median 12.7% and increased in 13 subjects with median 3.7%. Relative diastolic BP fall at night was negatively associated to CBF in temporal and infero-parietal areas. Higher proportion of subjects with increasing systolic BP during the 14-year period was observed in the subgroup with extreme nocturnal diastolic BP dip, irrespectively of BP values or prevalence of hypertension. Extreme nocturnal diastolic BP fall in a cohort of elderly men is correlated with focal changes in CBF. Further studies could explain if increasing BP in the elderly is a cause or result of pathological autoregulation, and if antihypertensive treatment increases nocturnal BP dip. [source]


    Platypus Pou5f1 reveals the first steps in the evolution of trophectoderm differentiation and pluripotency in mammals

    EVOLUTION AND DEVELOPMENT, Issue 6 2008
    Hitoshi Niwa
    SUMMARY Uterine nourishment of embryos by the placenta is a key feature of mammals. Although a variety of placenta types exist, they are all derived from the trophectoderm (TE) cell layer of the developing embryo. Egg-laying mammals (platypus and echidnas) are distinguished by a very short intrauterine embryo development, in which a simple placenta forms from TE-like cells. The Pou5f1 gene encodes a class V POU family transcription factor Oct3/4. In mice, Oct3/4 together with the highly conserved caudal -related homeobox transcription factor Cdx2, determines TE fate in pre-implantation development. In contrast to Cdx2, Pou5f1 has only been identified in eutherian mammals and marsupials, whereas, in other vertebrates, pou2 is considered to be the Pou5f1 ortholog. Here, we show that platypus and opossum genomes contain a Pou5f1 and pou2 homolog, pou2-related, indicating that these two genes are paralogues and arose by gene duplication in early mammalian evolution. In a complementation assay, we found that platypus or human Pou5f1, but not opossum or zebrafish pou2, restores self-renewal in Pou5f1 -null mouse ES cells, showing that platypus possess a fully functional Pou5f1 gene. Interestingly, we discovered that parts of one of the conserved regions (CR4) is missing from the platypus Pou5f1 promoter, suggesting that the autoregulation and reciprocal inhibition between Pou5f1 and Cdx2 evolved after the divergence of monotremes and may be linked to the development of more elaborate placental types in marsupial and eutherian mammals. [source]


    Regulation of cerebral blood flow in mammals during chronic hypoxia: a matter of balance

    EXPERIMENTAL PHYSIOLOGY, Issue 2 2010
    Philip N. Ainslie
    Respiratory-induced changes in the partial pressures of arterial carbon dioxide and oxygen play a major role in cerebral blood flow (CBF) regulation. Elevations in (hypercapnia) lead to vasodilatation and increases in CBF, whereas reductions in (hypocapnia) lead to vasoconstriction and decreases in CBF. A fall in (hypoxia) below a certain threshold (<40,45 mmHg) also produces cerebral vasodilatation. Upon initial exposure to hypoxia, CBF is elevated via a greater relative degree of hypoxia compared with hypocapnia. At this point, hypoxia-induced elevations in blood pressure and loss of cerebral autoregulation, stimulation of neuronal pathways, angiogenesis, release of adenosine, endothelium-derived NO and a variety of autocoids and cytokines are additional factors acting to increase CBF. Following 2,3 days, however, the process of ventilatory acclimatization results in a progressive rise in ventilation, which increases and reduces , collectively acting to attenuate the initial rise in CBF. Other factors acting to lower CBF include elevations in haematocrit, sympathetic nerve activity and local and endothelium-derived vasoconstrictors. Hypoxia-induced alterations of cerebrovascular reactivity, autoregulation and pulmonary vascular tone may also affect CBF. Thus, the extent of change in CBF during exposure to hypoxia is dependent on the balance between the myriad of vasodilators and constrictors derived from the endothelium, neuronal innervations and perfusion pressure. This review examines the extent and mechanisms by which hypoxia regulates CBF. Particular focus will be given to the marked influence of hypoxia associated with exposure to high altitude and chronic lung disease. The associated implications of these hypoxia-induced integrative alterations for the regulation of CBF are discussed, and future avenues for research are proposed. [source]


    The baroreflex is counteracted by autoregulation, thereby preventing circulatory instability

    EXPERIMENTAL PHYSIOLOGY, Issue 4 2004
    Roberto Burattini
    The aims of this study were (a) to apply in the animal with intact baroreflex a two-point method for estimation of overall, effective open-loop gain, G0e, which results from the combined action of baroregulation and total systemic autoregulation on peripheral resistance; (b) to predict specific baroreflex gain by correcting the effective gain for the autoregulation gain; and (c) to discuss why the effective gain is usually as low as 1,2 units. G0e was estimated from two measurements of both cardiac output, Q, and mean systemic arterial pressure, P: one in the reference state (set-point) and the other in a steady-state reached 1,3 min after a small cardiac output perturbation. In anaesthetized cats and dogs a cardiac output perturbation was accomplished by partial occlusion of the inferior vena cava and by cardiac pacing, respectively. Average (s.e.m.) estimates of G0e were 1.4 0.2 (n= 8) in the cat and 1.5 0.4 (n= 5) in the dog. The specific baroreflex open-loop gain, G0b, found after correction for total systemic autoregulation, was 3.3 0.4 in the cat and 2.8 0.8 in the dog. A model-based analysis showed that, with G0e as low as 1.4, the closed-loop response of P to a stepwise perturbation in Q results in damped oscillations that disappear in about 1 min. The amplitude and duration of these oscillations, which have a frequency of about 0.1 Hz, increase with increasing G0e and cause instability when G0e is about 3. We conclude that autoregulation reduces the effectiveness of baroreflex gain by about 55%, thereby preventing instability of blood pressure response. [source]


    Arterial Myogenic Properties of the Spontaneously Hypertensive Rat

    EXPERIMENTAL PHYSIOLOGY, Issue 5 2002
    Jennifer M. Hughes
    When subject to a transmural pressure gradient resistance arteries develop a spontaneous, intrinsically initiated contraction which varies according to the pressure stimulus and occurs in the absence of vasoconstrictor agonists. Such pressure-dependent active changes in vascular tone are indicative of the vascular myogenic response and contribute to autoregulation and the setting of total peripheral resistance and hence blood pressure regulation. The myogenic behaviour of blood vessels provides the background tone upon which other vasomotor influences act. Hypertension is associated with a raised vascular resistance and in this article the evidence for increased myogenic activity contributing to the raised vascular resistance is reviewed. Although there are some cases that provide evidence for exaggerated myogenic responsiveness in resistance arteries taken from hypertensive animals it is not possible to conclude that enhanced myogenic contractile responses within normal pressure ranges contribute to the raised total peripheral resistance. However, the myogenic tone of the resistance arteries of the various vascular beds is subject to differing modulatory influences in hypertensive animals and their normotensive controls which may contribute to the aetiology of hypertension. [source]


    Experimental and steady-state analysis of the GAL regulatory system in Kluyveromyces lactis

    FEBS JOURNAL, Issue 14 2010
    Venkat R. Pannala
    The galactose uptake mechanism in yeast is a well-studied regulatory network. The regulatory players in the galactose regulatory mechanism (GAL system) are conserved in Saccharomyces cerevisiae and Kluyveromyces lactis, but the molecular mechanisms that occur as a result of the molecular interactions between them are different. The key differences in the GAL system of K. lactis relative to that of S. cerevisiae are: (a) the autoregulation of KlGAL4; (b) the dual role of KlGal1p as a metabolizing enzyme as well as a galactose-sensing protein; (c) the shuttling of KlGal1p between nucleus and cytoplasm; and (d) the nuclear confinement of KlGal80p. A steady-state model was used to elucidate the roles of these molecular mechanisms in the transcriptional response of the GAL system. The steady-state results were validated experimentally using measurements of ,-galactosidase to represent the expression for genes having two binding sites. The results showed that the autoregulation of the synthesis of activator KlGal4p is responsible for the leaky expression of GAL genes, even at high glucose concentrations. Furthermore, GAL gene expression in K. lactis shows low expression levels because of the limiting function of the bifunctional protein KlGal1p towards the induction process in order to cope with the need for the metabolism of lactose/galactose. The steady-state model of the GAL system of K. lactis provides an opportunity to compare with the design prevailing in S. cerevisiae. The comparison indicates that the existence of a protein, Gal3p, dedicated to the sensing of galactose in S. cerevisiae as a result of genome duplication has resulted in a system which metabolizes galactose efficiently. [source]


    A steady-state modeling approach to validate an in vivo mechanism of the GAL regulatory network in Saccharomyces cerevisiae

    FEBS JOURNAL, Issue 20 2004
    Malkhey Verma
    Cellular regulation is a result of complex interactions arising from DNA,protein and protein,protein binding, autoregulation, and compartmentalization and shuttling of regulatory proteins. Experiments in molecular biology have identified these mechanisms recruited by a regulatory network. Mathematical models may be used to complement the knowledge-base provided by in vitro experimental methods. Interactions identified by in vitro experiments can lead to the hypothesis of multiple candidate models explaining the in vivo mechanism. The equilibrium dissociation constants for the various interactions and the total component concentration constitute constraints on the candidate models. In this work, we identify the most plausible in vivo network by comparing the output response to the experimental data. We demonstrate the methodology using the GAL system of Saccharomyces cerevisiae for which the steady-state analysis reveals that Gal3p neither dimerizes nor shuttles between the cytoplasm and the nucleus. [source]


    Autoregulation of the HAC1 gene is required for sustained activation of the yeast unfolded protein response

    GENES TO CELLS, Issue 2 2004
    Naoki Ogawa
    Eukaryotic cells respond to the accumulation of unfolded proteins in the endoplasmic reticulum (ER) by activating a transcriptional induction program termed the unfolded protein response (UPR). The transcription factor Hac1p responsible for the UPR in Saccharomyces cerevisiae is tightly regulated by a post-transcriptional mechanism. HAC1 mRNA must be spliced in response to ER stress to produce Hac1p, which then activates transcription via direct binding to the cis -acting UPR element (UPRE) present in the promoter regions of its target genes. Here, we show that the HAC1 promoter itself responds to ER stress to induce transcription of its downstream gene, similarly to the KAR2 promoter; the KAR2 gene represents a major target of the UPR. Consistent with this observation, the HAC1 promoter contains an UPRE-like sequence, which is necessary and sufficient for the induction and to which Hac1p binds directly. Cells expressing the HAC1 gene from a mutant HAC1 promoter lacking the HAC1 UPRE could not maintain high levels of either unspliced or spliced HAC1 mRNA and became sensitive to ER stress when insulted for hours. Based on these results, we concluded that autoregulation of the HAC1 genes is required for sustained activation of the UPR and sustained resistance to ER stress. [source]


    Neurokinin 3 Receptor Immunoreactivity in the Septal Region, Preoptic Area and Hypothalamus of the Female Sheep: Colocalisation in Neurokinin B Cells of the Arcuate Nucleus but not in Gonadotrophin-Releasing Hormone Neurones

    JOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2010
    M. Amstalden
    Recent evidence has implicated neurokinin B (NKB) in the complex neuronal network mediating the effects of gonadal steroids on the regulation of gonadotrophin-releasing hormone (GnRH) secretion. Because the neurokinin 3 receptor (NK3R) is considered to mediate the effects of NKB at the cellular level, we determined the distribution of immunoreactive NK3R in the septal region, preoptic area (POA) and hypothalamus of the ewe. NK3R cells and/or fibres were found in areas including the bed nucleus of the stria terminalis, POA, anterior hypothalamic and perifornical areas, dopaminergic A15 region, dorsomedial and lateral hypothalamus, arcuate nucleus (ARC) and the ventral premammillary nucleus. We also used dual-label immunocytochemistry to determine whether a neuroanatomical basis for direct modulation of GnRH neurones by NKB was evident. No GnRH neurones at any rostral-caudal level were observed to contain NK3R immunoreactivity, although GnRH neurones and fibres were in proximity to NK3R-containing fibres. Because NKB fibres formed close contacts with NKB neurones in the ARC, we determined whether these NKB neurones also contained immunoreactive NK3R. In luteal-phase ewes, 64% 11 of NKB neurones colocalised NK3R. In summary, NK3R is distributed in areas of the sheep POA and hypothalamus known to be involved in the control of reproductive neuroendocrine function. Colocalisation of NK3R in NKB neurones of the ARC suggests a potential mechanism for the autoregulation of this subpopulation; however, the lack of NK3R in GnRH neurones suggests that the actions of NKB on GnRH neurosecretory activity in the ewe are mediated indirectly via other neurones and/or neuropeptides. [source]


    Neuroimaging in Posterior Reversible Encephalopathy Syndrome

    JOURNAL OF NEUROIMAGING, Issue 2 2004
    C. Lamy
    ABSTRACT The terms posterior reversible leukoencephalopathy, reversibleposterior cerebral edema syndrome, and posterior reversibleencephalopathy syndrome(PRES) all refer to a clinicoradiologic entity characterized by headaches, confusion, visual disturbances, seizures, and posterior transient changes on neuroimaging. Clinical findings are not sufficiently specific to readily establish the diagnosis; in contrast, magnetic resonance imaging pattern is often characteristic and represents an essential component of the diagnosis of PRES. Typical lesions predominate in the posterior white matter, with some involvement of the overlying cortex; are hyperintense on T2-weighted images; and are usually hypointense or isointense on diffusion-weighted images, with an increase of the apparent diffusion coefficient, indicating vasogenic edema. The pathogenesis is incompletely understood, although it seems to be related to the breakthrough of autoregulation and endothelial dysfunction. Since its initial description, this syndrome has been subsequently described in an increasing number of medical conditions, including hypertensive encephalopathy, eclampsia, and the use of cytotoxic and immunosuppressive drugs. The diagnosis has important therapeutic and prognostic implications because the reversibility of the clinical and radiologic abnormalities is contingent on the prompt control of blood pressure and/or discontinuing the offending drug. On the contrary, when unrecognized, conversion to irreversible cytotoxic edema may occur. [source]


    Remifentanil and the brain

    ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2008
    V. FODALE
    Background and aim: Remifentanil is an ultra-short-acting opioid, increasingly used today in neuroanesthesia and neurointensive care. Its characteristics make remifentanil a potentially ideal agent, but previous data have cast a shadow on this opioid, supporting potentially toxic effects on the ischemic brain. The aim of the present concise review is to survey available up-to-date information on the effects of remifentanil on the central nervous system. Method: A MEDLINE search within the past seven years for available up-to-date information on remifentanil and brain was performed. Results: Concise up-to-date information on the effects of remifentanil on the central nervous system was reported, with a particular emphasis on the following topics: cerebral metabolism, electroencephalogram, electrocorticography, motor-evoked potentials, regional cerebral blood flow, cerebral blood flow velocity, arterial hypotension and hypertension, intracranial pressure, cerebral perfusion pressure, cerebral autoregulation, cerebrovascular CO2 reactivity, cerebrospinal fluid, painful stimulation, analgesia and hyperalgesia, neuroprotection, neurotoxicity and hypothermia. Conclusion: The knowledge of the influence of remifentanil on brain functions is crucial before routine use in neuroanesthesia to improve anesthesia performance and patient safety as well as outcome. [source]


    Regional cerebral blood flow autoregulation in patients with fulminant hepatic failure

    LIVER TRANSPLANTATION, Issue 6 2000
    Fin Stolze Larsen
    The absence of cerebral blood flow autoregulation in patients with fulminant hepatic failure (FHF) implies that changes in arterial pressure directly influence cerebral perfusion. It is assumed that dilatation of cerebral arterioles is responsible for the impaired autoregulation. Recently, frontal blood flow was reported to be lower compared with other brain regions, indicating greater arteriolar tone and perhaps preserved regional cerebral autoregulation. In patients with severe FHF (6 women, 1 man; median age, 46 years; range, 18 to 55 years), we tested the hypothesis that perfusion in the anterior cerebral artery would be less affected by an increase in mean arterial pressure compared with the brain area supplied by the middle cerebral artery. Relative changes in cerebral perfusion were determined by transcranial Doppler,measured mean flow velocity (Vmean), and resistance was determined by pulsatility index in the anterior and middle cerebral arteries. Cerebral autoregulation was evaluated by concomitant measurements of mean arterial pressure and Vmean in the anterior and middle cerebral arteries during norepinephrine infusion. Baseline Vmean was lower in the brain area supplied by the anterior cerebral artery compared with the middle cerebral artery (median, 47 cm/s; range, 21 to 62 cm/s v 70 cm/s; range 43 to 119 cm/s, respectively; P < .05). Also, vascular resistance determined by pulsatility index was greater in the anterior than middle cerebral artery (median, 1.02; range 1.00 to 1.37 v 0.87; range 0.75 to 1.48; P < .01). When arterial pressure was increased from 84 mm Hg (range 57 to 95 mm Hg) to 115 mm Hg (range, 73 to 130 mm Hg) during norepinephrine infusion, Vmean remained unchanged in 2 patients in the anterior cerebral artery, whereas it increased in the middle cerebral artery in all 7 patients. In the remaining patients, Vmean increased approximately 25% in both the anterior and middle cerebral arteries. Thus, this study could only partially confirm the hypothesis that autoregulation is preserved in the brain regions supplied by the anterior cerebral artery in patients with FHF. Although the findings of this small study need to be further evaluated, one should consider that autoregulation may be impaired not only in the brain region supplied by the middle cerebral artery, but also in the area corresponding to the anterior cerebral artery. [source]


    What's New in the Cerebral Microcirculation?

    MICROCIRCULATION, Issue 6 2001
    DONALD D. HEISTAD
    ABSTRACT The first part of this paper focuses on unusual aspects of the cerebral circulation. Cerebral vessels have less smooth muscle and adventitia than other vessels, and the endothelial blood-brain barrier is unique. Because the wall of the arteries is thin, one might expect that the vessels are especially vulnerable to rupture. Pressure in intracranial arteries, however, is lower than in other arteries, because resistance of larger cerebral arteries is remarkably high. The low pressure in cerebral arteries presumably protects against rupture of the vessels. The second part of the paper summarizes some new insights into regulation of cerebral circulation. One concept is that "breakthrough" of autoregulation, with dilatation of cerebral vessels at high levels of pressure, is an active process, rather than a passive phenomenon. This conclusion is based on the finding that inhibitors of calcium-dependent potassium channels greatly attenuate the cerebral vasodilator response during acute hypertension. The third part of the paper focuses on effects of gene transfer to cerebral blood vessels. Gene transfer to intracranial and extracranial vessels is feasible and vasomotor function can be altered. Gene transfer has proven to be useful to study vascular biology, and we are optimistic that the approach will ultimately lead to gene therapy. [source]


    NO message from muscle

    MICROSCOPY RESEARCH AND TECHNIQUE, Issue 3 2001
    Zarko Grozdanovic
    Abstract The synthesis of the free radical gas nitric oxide (NO) is catalyzed by the enzyme NO synthase (NOS). NOS converts arginine and molecular oxygen to NO and citrulline in a reaction that requires NADPH, FAD, FMN, and tetrahydrobiopterin as cofactors. Three types of NOS have been identified by molecular cloning. The activity of the constitutively expressed neuronal NOS (nNOS) and endothelial NOS (eNOS) is Ca2+/calmodulin-dependent, whereas that the inducible NOS (iNOS) is Ca2+ -insensitive. The predominant NOS isoform in skeletal muscle is nNOS. It is present at the sarcolemma of both extra- and intrafusal muscle fibers. An accentuated accumulation of nNOS is found in the endplate area. This strict sarcolemmal localization of nNOS is due its association with the dystrophin-glycoprotein complex, which is mediated by the syntrophins. The activity of nNOS in skeletal muscle is regulated by developmental, myogenic, and neurogenic influences. NO exerts several distinct effects on various aspects of skeletal muscle function, such as excitation-contraction coupling, mitochondrial energy production, glucose metabolism, and autoregulation of blood flow. Inside the striated muscle fibers, NO interacts directly with several classes of proteins, such as soluble guanylate cyclase, ryanodine receptor, sarcoplasmic reticulum Ca2+ -ATPase, glyceraldehyde-3-phosphate dehydrogenase, and mitochondrial respiratory chain complexes, as well as radical oxygen species. In addition, NO produced and released by contracting muscle fibers diffuses to nearby arterioles where it acts to inhibit reflex sympathetic vasoconstriction. Microsc. Res. Tech. 55:148,153, 2001. 2001 Wiley-Liss, Inc. [source]


    The cia operon of Streptococcus mutans encodes a unique component required for calcium-mediated autoregulation

    MOLECULAR MICROBIOLOGY, Issue 1 2008
    Xuesong He
    Summary Streptococcus mutans is a primary pathogen for dental caries in humans. CiaR and CiaH of S. mutans comprise a two-component signal transduction system (TCS) involved in regulating various virulent factors. However, the signal that triggers the CiaRH response remains unknown. In this study, we show that calcium is a signal for regulation of the ciaRH operon, and that a double-glycine-containing small peptide encoded within the ciaRH operon (renamed ciaX) mediates this regulation. CiaX contains a serine + aspartate (SD) domain that is shared by calcium-binding proteins. A markerless in-frame deletion of ciaX reduced ciaRH operon expression and diminished the calcium repression of operon transcription. Point mutations of the SD domain resulted in the same phenotype as the in-frame deletion, indicating that the SD domain is required for CiaX function. Further characterization of ciaX demonstrated that it is involved in calcium-mediated biofilm formation. Furthermore, inactivation of ciaR or ciaH led to the same phenotype as the in-frame deletion of ciaX, suggesting that all three genes are involved in the same regulatory pathway. Sequence analysis and real-time RT-PCR identified a putative CiaR binding site upstream of ciaX. We conclude that the ciaXRH operon is a three-component, self-regulatory system modulating cellular functions in response to calcium. [source]


    A subset of GAF domains are evolutionarily conserved sodium sensors

    MOLECULAR MICROBIOLOGY, Issue 2 2007
    Martin Cann
    Summary Most organisms maintain a transmembrane sodium gradient for cell function. Despite the importance of Na+ in physiology, no directly Na+ -responsive signalling molecules are known. The CyaB1 and CyaB2 adenylyl cyclases of the cyanobacterium Anabaena PCC 7120 are inhibited by Na+. A D360A mutation in the GAF-B domain of CyaB1 ablated cAMP-mediated autoregulation and Na+ inhibition. Na+ bound the isolated GAF domains of CyaB2. cAMP blocked Na+ binding to GAF domains but Na+ had no effect on cAMP binding. Na+ altered GAF domain structure indicating a mechanism of inhibition independent of cAMP binding. ,cyaB1 and ,cyaB2 mutant strains did not grow below 0.6 mM Na+ and ,cyaB1 cells possessed defects in Na+/H+ antiporter function. Replacement of the CyaB1 GAF domains with those of rat phosphodiesterase type 2 revealed that Na+ inhibition has been conserved since the eukaryotic/bacterial divergence. CyaB1 and CyaB2 are the first identified directly Na+ -responsive signalling molecules that function in sodium homeostasis and we propose a subset of GAF domains underpin an evolutionarily conserved Na+ signalling mechanism. [source]


    Function in Escherichia coli of the non-catalytic part of RNase E: role in the degradation of ribosome-free mRNA

    MOLECULAR MICROBIOLOGY, Issue 5 2002
    Anne Leroy
    Summary RNase E contains a large non-catalytic region that binds RNA and the protein components of the Escherichia coli RNA degradosome. The rne gene was replaced with alleles encoding deletions in the non-catalytic part of RNase E. All the proteins are stable in vivo. RNase E activity was tested using a PT7,lacZ reporter gene, the message of which is particularly sensitive to degradation because translation is uncoupled from transcription. The non-catalytic region has positive and negative effectors of mRNA degradation. Disrupting RhlB and enolase binding resulted in hypoactivity, whereas disrupting PNPase binding resulted in hyperactivity. Expression of the mutant proteins in vivo anticorrelates with activity showing that autoregulation compensates for defective function. There is no simple correlation between RNA binding and activity in vivo. An allele (rne131), expressing the catalytic domain alone, was put under Plac control. In contrast to rne+, low expression of rne131 severely affects growth. Even with autoregulation, all the mutants are less fit when grown in competition with wild type. Although the catalytic domain of RNase E is sufficient for viability, our work demonstrates that elements in the non-catalytic part are necessary for normal activity in vivo. [source]


    Polyadenylation of Escherichia coli transcripts plays an integral role in regulating intracellular levels of polynucleotide phosphorylase and RNase E

    MOLECULAR MICROBIOLOGY, Issue 5 2002
    Bijoy K. Mohanty
    Summary Polyadenylation in Escherichia coli has been implicated in the destabilization of a variety of transcripts. However, transiently increasing intracellular poly(A) levels has also been shown to stabilize the pnp and rne transcripts, leading to increased polynucleotide phosphorylase (PNPase) and RNase E levels respectively. Here, we show that the half-lives of both the pnp and rne transcripts are dependent on the intracellular level of polyadenylated transcripts. In addition, experiments using pnp,lacZ and rne,lacZ translational fusions demonstrate that the variations in transcript stability and protein levels arise from alterations in the autoregulation of both genes. Further support for this conclusion is provided by the fact that, in an rne mutant in which autoregulation is inactivated by deletion of most of the 5, untranslated region, variations in the level of polyadenylated transcripts no longer affect RNase E protein expression. Of even more interest is the fact that the presence of a functional degradosome is essential for RNase E to detect increased levels of poly(A). Thus, it appears that polyadenylation of transcripts in E. coli serves as a sensing mechanism by which the cell adjusts the levels of both RNase E and PNPase. [source]


    Plasticity of a transcriptional regulation network among alpha-proteobacteria is supported by the identification of CtrA targets in Brucella abortus

    MOLECULAR MICROBIOLOGY, Issue 4 2002
    Anne-Flore Bellefontaine
    Summary CtrA is a master response regulator found in many alpha-proteobacteria. In Caulobacter crescentus and Sinorhizobium meliloti, this regulator is essential for viability and is transcriptionally autoregulated. In C. crescentus, it is required for the regulation of multiple cell cycle events, such as DNA methylation, DNA replication, flagella and pili biogenesis and septation. Here, we report the characterization of the ctrA gene homologue in the ,2 -proteobacteria Brucella abortus, a facultative intracellular pathogen responsible for brucellosis. We detected CtrA expression in the main Brucella species, and its overproduction led to a phenotype typical of cell division defect, consistent with its expected role. A purified B. abortus CtrA recombinant protein (His6,CtrA) was shown to protect the B. abortus ctrA promoter from DNase I digestion, suggesting transcriptional autoregulation, and this protection was enhanced under CtrA phosphorylation on a conserved Asp residue. Despite the similarities shared by B. abortus and C. crescentus ctrA, the pathway downstream from CtrA may be distinct, at least partially, in both bacteria. Indeed, beside ctrA itself, only one (the ccrM gene) out of four B. abortus homologues of known C. crescentus CtrA targets is bound in vitro by phosphorylated B. abortus CtrA. Moreover, further footprinting experiments support the hypothesis that, in B. abortus, CtrA might directly regulate the expression of the rpoD, pleC, minC and ftsE homologues. Taken together, these results suggest that, in B. abortus and C. crescentus, similar cellular processes are regulated by CtrA through the control of distinct target genes. The plasticity of the regulation network involving CtrA in these two bacteria may be related to their distinct lifestyles. [source]


    Does dopexamine influence regional vascular tone and oxygenation during intestinal hypotension?

    ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2002
    S. Lehtipalo
    Background: Local effects of dopexamine on intestinal vascular tone and oxygenation were investigated during intestinal hypotension. To this end, we employed an experimental model, in which the superior mesenteric arterial pressure (PSMA) was controlled by an adjustable perivascular clamp. This approach enabled us to keep the intestinal perfusion pressure (IPP) constant in the face of any systemic circulatory alterations. Methods: In 11 barbiturate-anesthetized pigs, we instrumented the superior mesenteric circulation for assessments of vascular resistance (RMES), IPP, jejunal mucosal perfusion (Laser Doppler) and intestinal tissue oxygenation (microoximetry). Measurements were carried out before and during dopexamine infusions (0.5 and 1.0 gkg,1min,1) at a freely variable PSMA (i.e. the perivascular clamp fully open) and at a PSMA of 50 mmHg and 30 mmHg. Results: At a constant PSMA of 50 mmHg, dopexamine had no significant intestinal vascular effects. However, at a constant PSMA of 30 mmHg, both doses of dopexamine were associated with decreases in RMES. Effects of dopexamine on intestinal oxygen delivery and extraction were minimal during these procedures, while a minor decrease in intestinal tissue oxygen tension was observed during dopexamine administration at the lowest IPP level. Conclusion: At very low intestinal perfusion pressures (approximately 30 mmHg) dopexamine produces intestinal vasodilation in excess of what is produced by intrinsic autoregulation. This suggests that there is a vasodilatory reserve in the intestine under such conditions and that a pharmacological vasodilator like dopexamine may improve intestinal circulation during regional severe hypotension. [source]