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Vascular Homeostasis (vascular + homeostasi)

Distribution by Scientific Domains

Medical Sciences	87%

Selected Abstracts

Reduction of cerebral hyperperfusion by aminophylline: an example of pharmacological restoration of normal vascular homeostasis?

ACTA PAEDIATRICA, Issue 8 2000
HC Lou
No abstract is available for this article. [source]

Intracerebral large artery disease in Aicardi,Goutières syndrome implicates SAMHD1 in vascular homeostasis

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 8 2010
VENKATESWARAN RAMESH
Aim, To describe a spectrum of intracerebral large artery disease in Aicardi,Goutières syndrome (AGS) associated with mutations in the AGS5 gene SAMHD1. Method, We used clinical and radiological description and molecular analysis. Results, Five individuals (three males, two females) were identified as having biallelic mutations in SAMHD1 and a cerebral arteriopathy in association with peripheral vessel involvement resulting in chilblains and ischaemic ulceration. The cerebral vasculopathy was primarily occlusive in three patients (with terminal carotid occlusion and basal collaterals reminiscent of moyamoya syndrome) and aneurysmal in two. Three of the five patients experienced intracerebral haemorrhage, which was fatal in two individuals. Post-mortem examination of one patient suggested that the arteriopathy was inflammatory in origin. Interpretation, Mutations in SAMHD1 are associated with a cerebral vasculopathy which is likely to have an inflammatory aetiology. A similar disease has not been observed in patients with mutations in AGS1 to AGS4, suggesting a particular role for SAMHD1 in vascular homeostasis. Our report raises important questions about the management of patients with mutations in SAMHD1. [source]

The role of IGF-I and its binding proteins in the development of type 2 diabetes and cardiovascular disease

DIABETES OBESITY & METABOLISM, Issue 3 2008
Vivienne A. Ezzat
Patients with insulin resistance and type 2 diabetes have an excessive risk of cardiovascular disease (CVD); this increased risk is not fully explained by traditional risk factors such as hypertension and dyslipidaemias. There is now compelling evidence to suggest that abnormalities of insulin-like growth factor-I (IGF-I) and one of its binding proteins, insulin-like growth factor-binding protein-1 (IGFBP-1), occur in insulin-resistant states and may be significant factors in the pathophysiology of CVD. We reviewed articles and relevant bibliographies following a systematic search of MEDLINE for English language articles between 1966 and the present, using an initial search strategy combining the MeSH terms: IGF, diabetes and CVD. Our aim was first to review the role of IGF-I in vascular homeostasis and to explore the mechanisms by which it may exert its effects. We also present an overview of the physiology of the IGF-binding proteins, and finally, we sought to summarize the evidence to date describing the changes in the insulin/IGF-I/IGFBP-1 axis that occur in type 2 diabetes and CVD; in particular, we have focused on the potential vasculoprotective effects of both IGF-I and IGFBP-1. We conclude that this system represents an interesting and novel therapeutic target in the prevention of CVD in type 2 diabetes. [source]

Age-Related Changes in Phosphorylation of Endothelial Nitric Oxide Synthase in the Rat Penis

THE JOURNAL OF SEXUAL MEDICINE, Issue 3 2005
Biljana Musicki PhD
ABSTRACT Aim., Aging is associated with erectile dysfunction (ED) attributed to reduced nitric oxide synthase (NOS) activity and nitric oxide bioavailability. However, the mechanism for this effect has not been fully investigated. We evaluated (i) whether age-related ED involves dysregulation of endothelial NOS (eNOS) phosphorylation; and (ii) whether vascular endothelial growth factor (VEGF) exerts erectile effects and operates via eNOS phosphorylation in aged rats. Methods., Male Fischer 344 "young" (4-month-old) and "aged" (19-month-old) rats were used. Electrical stimulation of the cavernous nerve (CNS) was performed to generate penile erection. Erectile response in the presence of rhVEGF165 was evaluated by intracavernosal pressure monitoring 25 minutes after intracavernosal injection of VEGF. Penes were excised at baseline, with or without rhVEGF treatment, and after CNS for Western immunoblot of phospho-eNOS (Ser-1177 and Thr-495), phospho-Akt, and eNOS. Results., Erectile response was significantly reduced in aged rats compared with young rats. Phospho-eNOS (Ser-1177) and phospho-Akt were significantly reduced, while phospho-eNOS (Thr-495) was significantly increased, in the aged penis at baseline and after CNS. rhVEGF significantly improved erection and reversed downregulated Ser-1177, but not upregulated Thr-495 phosphorylation, on eNOS in aged penes. eNOS protein was significantly increased in aged penes. Conclusions., Age-related ED is associated with eNOS inactivation through a decrease in phosphorylation of its positive regulatory site (Ser-1177) and an increase in phosphorylation of its negative regulatory site (Thr-495) in the penis. Altered phosphorylation/constitutive activation of eNOS by fluid shear stress may be a major determinant of compromised vascular homeostasis of the aged penis. The finding that VEGF rapidly induces erection and partly corrects alterations in eNOS phosphorylation in the aged rat penis suggests impaired eNOS activation by deficient endogenous VEGF and supports the potential for growth factor therapy in the treatment of age-related ED. [source]

Oxidative stress, endothelial function and coenzyme Q10

BIOFACTORS, Issue 1-4 2008
Romualdo Belardinelli
Abstract Reactive oxygen species seem to play an important role in vascular homeostasis. In conditions of high oxidative stress, such as chronic heart failure and multiple coronary risk factors, the rate of inactivation of nitric oxide to peroxynitrite by superoxide anions may be reduced by CoQ10, which can also protect against nitrosative damage. CoQ10 may also influence vascular function indirectly via inhibition of oxidative damage to LDL. Patients with lower levels of extracellular superoxide dismutase (ecSOD) demonstrate greater improvements than patients with normal ec-SOD levels, suggesting that the higher the oxidative stress the greater the improvement in the endothelium-dependent relaxation after the administration of a compound with antioxidant properties like CoQ10. Future studies are needed to inquire whether these effects may translate into benefits in clinical practice. [source]

Reciprocal regulation of human soluble and particulate guanylate cyclases in vivo

BRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2006
M Madhani
Background & purpose: We demonstrated previously that reciprocal regulation of soluble (sGC) and particulate (pGC) guanylate cyclases by NO and natriuretic peptides coordinates cyclic cGMP-mediated vasodilatation in vitro. Herein, we investigated whether such an interaction contributes to vascular homeostasis in mice and humans in vivo. Experimental approach: Mean arterial blood pressure (MABP) changes in anaesthetized mice were monitored in response to i.v. administration of cGMP- and cAMP-dependent vasodilators in wild-type (WT), endothelial NO synthase (eNOS) and natriuretic peptide receptor (NPR)-A knockout mice. Forearm blood flow (FBF) in response to intra-brachial infusion of ANP (25, 50, 100, 200 pmol min -1) in the absence and presence of the NOS inhibitor NG -methyl-L-arginine (L-NMA; 4 ,mol min -1) and the control constrictor noradrenaline (240 pmol min -1) was assessed in healthy volunteers. Key results: Sodium nitroprusside (SNP; NO-donor) and atrial natriuretic peptide (ANP) produced dose-dependent reductions in MABP in WT animals that were significantly enhanced in eNOS KO mice. In NPR-A K mice, SNP produced a dose-dependent reduction in MABP that was significantly greater than that in WT mice. Responsiveness to the cAMP-dependent vasodilator epoprostenol was similar in WT, eNOS KO and NPR-A KO animals. ANP caused vasodilatation of the forearm resistance vasculature that was significantly greater in individuals lacking endothelium-derived NO (i.e. L-NMA treated). Conclusions & implications: These data demonstrate that crosstalk occurs between the NO-sGC and ANP-pGC pathways to regulate cGMP-dependent vasodilatation in vivo in both mice and humans. These findings have implications for understanding the link between natriuretic peptide activity and cardiovascular risk. British Journal of Pharmacology (2006) 149, 797,801. doi:10.1038/sj.bjp.0706920 [source]

C-peptide: new findings and therapeutic implications in diabetes

CLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 4 2004
John Wahren
Summary In contrast to earlier views, new data indicate that proinsulin C-peptide exerts important physiological effects and shows the characteristics of an endogenous peptide hormone. C-peptide in nanomolar concentrations binds specifically to cell membranes, probably to a G-protein coupled receptor. Ca2+ - and MAP-kinase dependent signalling pathways are activated, resulting in stimulation of Na+, K+ -ATPase and endothelial nitric oxide (NO) synthase, two enzyme systems known to be deficient in diabetes. C-peptide may also interact synergistically with insulin signal transduction. Studies in intact animals and in patients with type 1 diabetes have demonstrated multifaceted effects. Thus, C-peptide administration in streptozotocin-diabetic animals results in normalization of diabetes-induced glomerular hyperfiltration, reduction of urinary albumin excretion and diminished glomerular expansion. The former two effects have also been observed in type 1 diabetes patients given C-peptide in replacement dose for up to 3 months. Peripheral nerve function and structure are likewise influenced by C-peptide administration; sensory and motor nerve conduction velocities increase and nerve structural changes are diminished or reversed in diabetic rats. In patients with type 1 diabetes, beneficial effects have been demonstrated on sensory nerve conduction velocity, vibration perception and autonomic nerve function. C-peptide also augments blood flow in several tissues in type 1 diabetes via its stimulation of endothelial NO release, emphasizing a role for C-peptide in maintaining vascular homeostasis. Continued research is needed to establish whether, among the hormones from the islets of Langerhans, C-peptide is the ugly duckling that , nearly 40 years after its discovery , may prove to be an endogenous peptide hormone of importance in the treatment of diabetic long-term complications. [source]