Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in systolic blood pressure (SBP), heart rate (HR), heart rate and plasma renin concentration (PRC) have been compared in three different groups of rats between the ages of 5 and 20 weeks. The groups were: spontaneously hypertensive rats (SHRs), atenolol-treated SHRs (200 mg/kg/day orally throughout the 15 weeks) and normotensive rats of the same strain (WKYs). Treatment with atenolol markedly inhibited the onset of genetic hypertension, reduced HR and PRC from the outset and diminished the heart weight/body weight ratio. Comparison of changes in these parameters in atenolol-treated SHRs, control SHRs and WKYs strongly suggests that the mechanism of atenolol's preventive action against hypertension development in SHRs primarily involves its effects on heart and on the renin--angiotensin system.
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PMID:Chronic atenolol treatment and hypertension development in spontaneously hypertensive rats. 63 Nov 88

Under inactin anesthesia, intravenous infusion of [Sar1,Thr8]angiotensin II produced a hypotensive effect in young spontaneously hypertensive rats (SHR) treated with furosemide and in mature SH rats fed a low-sodium diet. The angiotensin antagonist also lowered blood pressure of young and mature SH rats receiving a normal diet. Deoxycorticosterone acetate (DOCA) plus saline reversed the hypotensive effect of [Saru,Thr8]angiotensin II in young SH rats, but did not do so in mature SH rats. Plasma renin activity (PRA) was not significantly changed by anesthesia. Furosemide or the low-sodium diet significantly increased PRA in young and mature SH rats. In contrast, DOCA plus saline significantly reduced PRA in both young and mature SH rats. However, there was no correlation between PRA and the action of the angiotensin II antagonist. These data suggest that the renin-angiotensin system is involved in genetic hypertension.
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PMID:Hypotensive effect of [Sar1,Thr8]angiotensin II in spontaneously hypertensive sodium-depleted rats. 64 84

1. Strains of spontaneously hypertensive and normotensive rats were selected by repeated inbreeding. 2. Brief ether anesthesia was shown to produce a two- to three-fold increase in plasma renin activity in both strains. 3. Plasma renin activity was significantly higher in young spontaneously hypertensive than in normotensive rats of the same age (5-7 weeks). After the ninth week plasma renin activity decreased and, at week 45, became significantly lower in hypertensive than in normotensive rats. 4. When hypertension was established a significant inverse relationship was found between plasma renin activity and systolic blood pressure in spontaneously hypertensive and in normotensive rats. 5. It seems unlikely that the renin-angiotensin system plays a major role in the maintenance of the established spontaneous hypertension in this strain. However, renin hypersecretion may be important in the early pre-hypertensive stage of genetic hypertension in rats.
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PMID:Plasma renin activity as a function of age in two new strains of spontaneously hypertensive and normotensive rats. 125 23

The brain is one of the organs where an intrinsic renin-angiotensin system (RAS) has been described. Stimulation of circumventricular or brainstem angiotensin II (Ang II) receptors engenders a distinct pattern of cardiovascular, endocrine, and behavioral responses featuring blood pressure increase, attenuation of the baroreceptor reflex, drinking, release of pituitary hormones such as vasopressin, oxytocin, and ACTH, and natriuresis. In contrast to most of the other central actions of Ang II, the natriuretic effect cannot be elicited by Ang II as a circulating hormone. Recently, we have shown that stimulation of Ang II AT-1 receptors in the circumventricular organs causes a selective release of norepinephrine (NE) in the paraventricular nucleus (PVN) and in the supraoptic nucleus (SON). As vasopressin is also released from the PVN and SON, it is possible that the Ang II-NE interaction is involved in the release of vasopressin, thereby contributing to central blood pressure regulation and volume control. Finally, a substantial body of results suggests that an overactivity of the brain renin-angiotensin system is one of the contributors to genetic hypertension. However, this idea needs further confirmation.
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PMID:Role of brain angiotensin in cardiovascular regulation. 138 68

The cardiac interstitium is composed of non-myocyte cells and a structural fibrillar protein network which plays a dominant role in governing the structure, architecture, and mechanical behaviour of the myocardium. Herein we review the fibrillar collagen network, its various components, and the functions they serve in the normal and structurally remodelled myocardium in arterial hypertension. The heterogeneity in myocardial structure, created by the altered behaviour of non-myocyte cells, particularly cardiac fibroblasts, which are responsible for collagen synthesis or degradation and thereby fibrous tissue accumulation, is a major determinant for the appearance of diastolic dysfunction and ultimately systolic myocardial failure. Regulatory mechanisms related to this fibrous tissue response are reviewed to draw attention to the hitherto neglected role of cardiac fibroblasts in mediating adverse structural remodelling of the myocardium and showing how this can be prevented through the use of pharmacological agents that interfere with the regulation of the myocardial collagen matrix. Several lines of evidence suggest that circulating and tissue renin-angiotensin-aldosterone systems (RAAS) are involved in the structural remodelling of the non-myocyte compartment. These include the cardioprotective effects of angiotensin converting enzyme (ACE) inhibition and aldosterone receptor antagonism that were found to prevent myocardial fibrosis in the rat with renovascular hypertension. In the rat with genetic hypertension, established left ventricular hypertrophy and abnormal myocardial diastolic stiffness due to interstitial fibrosis, RAAS inhibition resulted in restoration of myocardial structure and function to normal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myocardial collagen matrix remodelling in arterial hypertension. 139 56

The hereditary nature of familial hypertension has been clearly established by a number of clinical studies. About 30% of the blood pressure variance can be attributed to genetic factors. As a consequence, the relative risk for developing coronary artery disease or cardiovascular death is increased in patients with a family history of hypertension and cardiovascular disease. Patients with such familial history should be considered at the same risk as those who have independent epidemiologic risk factors. The development of molecular genetics allows establishment of a link between high blood pressure, intermediate phenotypes, and the genes involved in blood pressure regulation. Gene markers should be available in the near future that will help to identify patients predisposed to hypertension. The genes of the renin-angiotensin-aldosterone system are good examples of candidate genes whose products are known to participate in blood pressure regulation. The possible involvement of these genes in essential hypertension is critically analyzed.
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PMID:Can the genetic factors influence the treatment of systemic hypertension? The case of the renin-angiotensin-aldosterone system. 141 20

Essential hypertension is a highly hereditable disorder in which genetic influences predominate over environmental factors. The molecular genetic profiles which predispose to essential hypertension are not known. In rats with genetic hypertension, there is some recent evidence pointing to linkage of renin gene alleles with blood pressure. The genes for renin and antithrombin III belong to a conserved synteny group which, in humans, spans the q21.3-32.3 region of chromosome I and, in rats, is linkage group X on chromosome 13. The present study examined the association of particular human renin gene (REN) and antithrombin III gene (AT3) polymorphisms with essential hypertension by comparing the frequency of specific alleles for each of these genes in 50 hypertensive offspring of hypertensive parents and 91 normotensive offspring of normotensive parents. In addition, linkage relationships were examined in hypertensive pedigrees with multiple affected individuals. Alleles of a REN HindIII restriction fragment length polymorphism (RFLP) were detected using a genomic clone, lambda HR5, to probe Southern blots of HindIII-cut leucocyte DNA, and those for an AT3 PstI RFLP were detected by phATIII 113 complementary DNA probe. The frequencies of each REN allele in the hypertensive group were 0.76 and 0.24 compared with 0.74 and 0.26 in the normotensive group. For AT3, hypertensive allele frequencies were 0.49 and 0.51 compared with normotensive values of 0.54 and 0.46. These differences were not significant by chi 2 analysis (P greater than 0.2).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Association and linkage analyses of restriction fragment length polymorphisms for the human renin and antithrombin III genes in essential hypertension. 168 42

The role of renin-angiotensin system in generation of genetic hypertension is unclear. Renal renin secretion was examined in renal superficial cortical slices from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) at 4 wk (prehypertensive), 6 wk (early hypertensive), and 12 wk (established hypertension) of age. Basal renin release in SHR was greater at 4 wk (749 +/- 55 vs. 480 +/- 50 ng/mg, P less than 0.005) and at 6 wk (428 +/- 70 vs. 266 +/- 60 ng/mg, P less than 0.02). Basal renin release declined by 43% between 4 and 6 wk and by 34% between 6- and 12-wk time periods in SHR. In SHR and WKY at all ages, renin responses to stimulation with isoproterenol (ISO, 10(-5) and 10(-6) M, respectively) were similar. Angiotensin II (ANG II) resulted in a significant reduction in renin release in both SHR and WKY at 10(-7) M in all age groups. The ANG II-induced percent change in renin release from control of SHR was less compared with WKY rats at 10(-8) and 10(-9)M at 4 wk of age. When ANG II was tested in presence of beta-adrenergic stimulation, a comparable renin inhibitory response was observed in both SHR and WKY. The number of ANG II-binding sites in proximal tubular brush-border membrane (BBM) was increased in SHR vs. WKY rats (458 +/- 18 vs. 235 +/- 12 fmol ANG II/mg BBM protein, P less than 0.001) at 4 wk of age. These data document increased basal renin release and ANG II-binding sites in proximal tubular BBM in 4 wk SHR compared with age-matched WKY rat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ontogeny of renal renin release in spontaneously hypertensive rat and Wistar-Kyoto rat. 184 63

Our study examines the long-term cardiovascular effects after a brief period of angiotensin converting enzyme (ACE) inhibitor treatment in young spontaneously hypertensive rats (SHR). SHR were treated with perindopril (3 mg/kg/day) by gavage from 2 to 6, from 6 to 10, or from 2 to 10 weeks of age. Systolic blood pressure was measured in the tail weekly until 25 weeks of age. Corresponding control groups received distilled water for the same periods. In each treatment group blood pressure was reduced significantly during treatment, rose when treatment stopped, but plateaued significantly below control SHR thereafter. This difference in blood pressure at 25 weeks of age was due to reduced total peripheral resistance as determined by microsphere methods, but plasma renin activity and angiotensin II concentrations were not different. Cardiac hypertrophy was also reduced in treated SHR. In a separate experiment, perindopril treatment from 6 to 10 weeks of age resulted in a significant reduction in the media/lumen ratios of mesenteric resistance vessels at 32 weeks of age. Concomitant administration of angiotensin II with perindopril from 6 to 10 weeks of age not only prevented the long-term effects on blood pressure seen with perindopril treatment alone but was associated with cardiovascular hypertrophy in excess of untreated control SHR. Finally, perindopril given for a shorter period (6 to 7 weeks) or later in life (20 to 24 weeks) had no significant long-term effects on blood pressure. These results demonstrate that a 4-week period of ACE inhibitor treatment in young SHR is sufficient to prevent the full expression of genetic hypertension and cardiovascular hypertrophy and that angiotensin II might be important in the development of hypertension in this model, its role in later life being less important.
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PMID:Brief angiotensin converting enzyme inhibitor treatment in young spontaneously hypertensive rats reduces blood pressure long-term. 224 28

Erythrocyte Na-K cotransport is high and genetically correlated to hypertension in Milan hypertensive strain (MHS) rats. In man there is a substantial overlap of individual values between essential hypertensives and controls. However, the findings in rat strains with different types of genetic hypertension suggest that Na-K cotransport studies may throw light on the different pathogenetic mechanisms of the human disease. In 28 normotensive and 22 hypertensive families the midparent-offspring correlation of Na-K cotransport values was significant only in hypertensive families (r = 0.48) and not significant in normotensive ones (r = 0.06), indicating genetic polymorphism for its phenotypic expression only in the hypertensives. In 189 essential hypertensives and 109 normotensives carefully selected from a population-based screening in order to exclude uneven sampling bias, analysis for the bimodality of the distribution of Na-K cotransport clearly showed that normotensives are distributed unimodally and hypertensives bimodally, with nadir of the distributions at about 450 mumols (1 RBC/h). Dividing the hypertensives according to Na-K cotransport value, the high Na-K cotransport subgroup has lower fractional percent excretion of uric acid and plasma renin activity. These data suggest that the high Na-K cotransport subgroup has peculiar characteristics of greater proximal tubular reabsorption (lower fractional excretion of uric acid) that may cause body volume expansion (lower plasma renin activity).
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PMID:Genetic polymorphism of Na-K cotransport in essential hypertension. 225 61


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