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Hypertrophic Effect (hypertrophic + effect)

Distribution by Scientific Domains
Medical Sciences50%

Selected Abstracts

The Transcriptional Coactivator p300 Plays a Critical Role in the Hypertrophic and Protective Pathways Induced by Phenylephrine in Cardiac Cells but Is Specific to the Hypertrophic Effect of Urocortin

CHEMBIOCHEM, Issue 1 2005
Sean M. Davidson Dr.
Abstract Anacardic acid is an alkylsalicylic acid obtained from cashew-nut-shell liquid, and is a potent inhibitor of p300 histone acetyl-transferase (HAT) activity. We have used anacardic acid to prevent the induction of hypertrophy in isolated neonatal rat cardiomyocytes. Hypertrophy was detected as an increase in cell size, the rearrangement of sarcomeres into a striated pattern, and the induction of embryonic genes ,-MHC and ANF. p300 inhibition was equally effective at preventing hypertrophy whether it was induced by treatment with the ,1-adrenergic agonist, phenylephrine, or by treatment with urocortin, a member of the corticotrophin-releasing-factor family, which stimulates specific G protein-coupled receptors. Spiruchostatin A is a natural-product inhibitor of histone deacetylases (HDAC) similar to the depsipeptide FK228 molecule. We have recently synthesized spiruchostatin A and now show that, although HDACs act in opposition to HATs, spiruchostatin A has the same effect as anacardic acid, that is, it prevents the induction of hypertrophy in response to phenylephrine or urocortin. Pretreatment with either phenylephrine or urocortin reduced the extent of death observed after the exposure of isolated cardiomyocytes to simulated ischaemia and reoxygenation. Inhibition of p300 or HDAC activity eliminated the protection conferred by phenylephrine; however, it did not affect the protection conferred by urocortin. Therefore, it might eventually be possible to use chemical inhibitors such as these in a therapeutic setting to dissociate the protective effect and hypertrophic effect of urocortin, enhancing the survival of cardiomyocytes exposed to transient ischemia, while inhibiting the hypertrophic pathway that would otherwise be induced concurrently. [source]

Cardiac dysfunction during exercise in patients with primary hyperparathyroidism

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 9 2000
I.-L. Nilsson
Background ,Non-traditional' manifestations of primary hyperparathyroidism (HPT) are controversial, and include morbidity, mortality and risk factors for cardiovascular diseases with some prospects of normalization by parathyroidectomy (PTX). This study evaluated previously unexplored data on cardiac function during exercise in HPT. Methods Thirty patients with HPT (mean(s.d.) serum calcium 2·96(0·24) mmol l,1) and 30 normocalcaemic controls (selected randomly from the background population, and matched for age and sex) underwent exercise testing, echocardiography and 24-h ambulatory blood pressure recordings before and a mean of 13 months after PTX. Results HPT was associated with higher systolic blood pressure during exercise (mean(s.d.) 223(28) versus 203(33) mmHg; P = 0·02), which correlated to the left ventricular (LV) mass and serum PTH (P = 0·014, P = 0·004); higher LV mass in men (mean(s.d.) 142(20) versus 113(28) g m,2), which might relate to the hypertrophic effect of PTH; and increased LV isovolumic relaxation times (mean(s.d.) 102(19) versus 91(15) ms; P = 0·018), indicating LV diastolic dysfunction. ST depression during exercise decreased significantly (mean(s.d.) , 1·0(0·9) versus 0·7(0·5) mm; P = 0·028) and LV mass declined in proportion with the time after PTX (P = 0·04 in men). PTX also affected systolic functions, as fractional shortening, atrioventricular plane displacement and systolic index decreased in men (P = 0·05, P = 0·04, P = 0·04). Twenty-four-hour blood pressures were higher in HPT (P = 0·008), when subjects on ,-blockers (seven patients, five controls) were excluded, and were unaltered by PTX. Conclusion LV systolic and diastolic dysfunction occurs in HPT. The diastolic dysfunction seems to diminish with time after PTX, while the positive inotropic effect of calcium in itself may alleviate the systolic dysfunction. © 2000 British Journal of Surgery Society Ltd [source]

The Transcriptional Coactivator p300 Plays a Critical Role in the Hypertrophic and Protective Pathways Induced by Phenylephrine in Cardiac Cells but Is Specific to the Hypertrophic Effect of Urocortin

CHEMBIOCHEM, Issue 1 2005
Sean M. Davidson Dr.
Abstract Anacardic acid is an alkylsalicylic acid obtained from cashew-nut-shell liquid, and is a potent inhibitor of p300 histone acetyl-transferase (HAT) activity. We have used anacardic acid to prevent the induction of hypertrophy in isolated neonatal rat cardiomyocytes. Hypertrophy was detected as an increase in cell size, the rearrangement of sarcomeres into a striated pattern, and the induction of embryonic genes ,-MHC and ANF. p300 inhibition was equally effective at preventing hypertrophy whether it was induced by treatment with the ,1-adrenergic agonist, phenylephrine, or by treatment with urocortin, a member of the corticotrophin-releasing-factor family, which stimulates specific G protein-coupled receptors. Spiruchostatin A is a natural-product inhibitor of histone deacetylases (HDAC) similar to the depsipeptide FK228 molecule. We have recently synthesized spiruchostatin A and now show that, although HDACs act in opposition to HATs, spiruchostatin A has the same effect as anacardic acid, that is, it prevents the induction of hypertrophy in response to phenylephrine or urocortin. Pretreatment with either phenylephrine or urocortin reduced the extent of death observed after the exposure of isolated cardiomyocytes to simulated ischaemia and reoxygenation. Inhibition of p300 or HDAC activity eliminated the protection conferred by phenylephrine; however, it did not affect the protection conferred by urocortin. Therefore, it might eventually be possible to use chemical inhibitors such as these in a therapeutic setting to dissociate the protective effect and hypertrophic effect of urocortin, enhancing the survival of cardiomyocytes exposed to transient ischemia, while inhibiting the hypertrophic pathway that would otherwise be induced concurrently. [source]

Endothelin ETA receptor antagonism does not attenuate angiotensin II-induced cardiac hypertrophy in vivo in rats

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2003
HR De Smet
Summary 1.,Angiotensin (Ang) II causes cardiac hypertrophy in vitro and in vivo. It also stimulates the release of endothelin (ET)-1. Endothelin-1 induces hypertrophy of cardiomyocytes in vitro. 2.,In the present study, we examined whether the cardiac hypertrophic action of AngII in vivo was mediated by ET-1 via ETA receptors. We also determined whether arginine vasopressin (AVP), another ET-1 stimulator, could cause cardiac hypertrophy in vivo through an ET-1-dependent pathway. 3.,In Sprague-Dawley rats (n = 8 per group), we determined whether the orally administered ETA receptor antagonist BMS 193884 could attenuate the cardiac hypertrophic effect of: (i) i.v. AngII infusion at either 100 or 200 ng/kg per min, i.v., for 1 week; (ii) AngII infusion at 100 ng/kg per min, i.v., for 2 weeks; and (iii) AVP infusion at either 2 or 10 ng/kg per min, i.v., for 1 week. Mean arterial pressure and heart rate were also measured. 4.,Infusion with AngII for both 1 and 2 weeks increased left ventricular weight. Only AngII infusion at 200 ng/kg per min for 1 week increased blood pressure. Endothelin ETA receptor blockade did not attenuate the left ventricular hypertrophy, even though it reduced the hypertensive effect of AngII. Arginine vasopressin increased blood pressure, but did not cause cardiac hypertrophy. 5.,We showed that AngII can cause cardiac hypertrophy through a direct, blood pressure-independent effect on the heart. Endothelin-1 did not mediate the cardiac hypertrophic effect of AngII through ETA receptors. This may indicate the involvement of ETB receptors in this model of cardiac hypertrophy. Arginine vasopressin did not cause cardiac hypertrophy in vivo. [source]