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)

Plasma endothelin concentrations were evaluated in 53 chronic, congestive heart failure (CHF) patients with or without history of systemic hypertension, as well as in 9 with hypertension only and in 22 healthy control subjects. Plasma renin, aldosterone and atrial natriuretic peptide, as well as clinical and hemodynamic data were determined. In patients with CHF, big endothelin-1 was, independent of hypertension history, significantly greater than in hypertensive patients with normal cardiac function and in control subjects (both p < 0.0001). Patients with severe CHF had significantly greater big endothelin-1 values than did those with moderate CHF. During 12-month follow-up, 11 patients with CHF underwent heart transplantation, and 9 died; these patients had significantly greater big endothelin-1 concentrations than did the 33 clinically stable patients (p < 0.001). Big endothelin-1 and atrial natriuretic peptide correlated with right atrial pressure, pulmonary capillary wedge pressure, left ventricular ejection fraction, effort capacity and severity of CHF (New York Heart Association functional class).
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PMID:Plasma big endothelin-1 concentrations in congestive heart failure patients with or without systemic hypertension. 849 69

The renin-angiotensin system and endothelin are important regulators of the cardiovascular system. Although increased production of endothelin-1 (ET-1) is reported in patients with heart failure, the detailed mechanism remains to be determined. To elucidate the relationship between the renin-angiotensin system and ET-1 in hypertensive heart failure, we evaluated the effects of long-term treatment with imidapril, an angiotensin converting enzyme (ACE) inhibitor, on preproET-1, endothelin A receptor (ETAR), and ACE mRNA expression in the left ventricle and evaluated these in relation to myocardial remodeling in the failing heart of Dahl salt-sensitive (DS) hypertensive rats fed a high salt diet. In DS rats fed an 8% NaCl diet after the age of 6 weeks, a stage of concentric left ventricular hypertrophy at 11 weeks (DSLVH) was followed by a distinct stage of left ventricular failure with chamber dilatation at 18 weeks (DSHF). Imidapril (DSHF-IM, n = 8, 1 mg/kg/day, subdepressor dose) or vehicle (DSHF-V, n = 8) was given from stage DSLVH to DSHF for 7 weeks, and age-matched (18 weeks) Dahl salt-resistant rats fed the same diet served as the control group (DR-C, n = 8). In both groups, blood pressure was similar and significantly higher than in DR-C. Markedly increased left ventricular end-diastolic diameter and reduced fractional shortening in DSHF-V was significantly ameliorated in DSHF-IM using transthoracic echocardiography. The preproET-1, ETAR, and ACE mRNA levels in the left ventricle were significantly increased in DSHF-V compared with DR-C, and significantly suppressed in DSHF-IM compared with DSHF-V. DSHF-V demonstrated a significant increase in the wall-to-lumen ratio and perivascular fibrosis in coronary arterioles, and myocardial fibrosis, with all these parameters being significantly improved by imidapril. In conclusion, myocardial remodeling and heart failure in DS rats fed a high salt diet were significantly ameliorated by a subdepressor dose of imidapril, which may be attributable to a decrease in ET-1 mRNA expression and angiotensin II in the left ventricle.
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PMID:Effects of imidapril on endothelin-1 and ACE gene expression in failing hearts of salt-sensitive hypertensive rats. 1104 Nov 63

The single oral administration of a mixed endothelin-A-and -B- (ETA/ETB) receptor antagonist, J-104132 (L-753,037) decreased the blood pressure in conscious spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP) and Dahl salt-sensitive hypertensive rats fed high-salt diet (DS-H) at doses of 3 and 10 mg/kg, with a duration of approximately 24 h. The magnitude of the antihypertensive effects was greater in DS-H than in SHR and SHRSP Preproendothelin-1 mRNA expression in the kidney and aorta was greater (about twofold) in DS-H than that in nonnotensive Dahl salt-resistant rats fed high-salt diet (DR-H), while there was no difference in preproendothelin-1 mRNA expression between SHR and Wistar Kyoto rats (WKY). An AT1-receptor antagonist, MK-954 (Losartan), also attenuated hypertension in SHR and SHRSP at oral doses of 3 and 10 mg/kg, but bad no effect in DS-H. The concomitant treatment with MK-954 and J-104132 showed additive antihypertensive effects in SHR and SHRSP. In DS-H, MK-954 potentiated the antihypertensive effects of J-104132. From these results, we suggest that: (1) the contribution of endothelin (ET) to the maintenance of hypertension is greater in salt-sensitive hypertensive models than in SHR and SHRSP; (2) the antihypertensive efficacy of ETA/ETB blockade is augmented by AT1-receptor blockade; (3) ET blockers alone or in combination with AT1 antagonists could be useful in the treatment of hypertension for patients who do not respond adequately to renin-angiotensin system inhibitors alone.
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PMID:Antihypertensive effects of a mixed endothelin-A- and -B-receptor antagonist, J-104132, were augmented in the presence of an AT1 -receptor antagonist, MK-954. 1107 14

We have recently reported that endothelin-1 (ET-1), which is increased in the arteries of deoxycorticosterone acetate (DOCA)-salt hypertensive rats, stimulates superoxide production. However, the humoral mechanisms responsible for ET-1-induced superoxide formation in low-renin models of hypertension, such as DOCA-salt hypertension, remain undefined. Vasopressin is known to upregulate vascular preproET-1 gene expression in DOCA-salt rats, an effect that is absent in vasopressin-deficient Brattleboro rats treated with DOCA-salt. The present study tested the hypothesis that vasopressin contributes to ET-1-induced vascular superoxide production in DOCA-salt hypertensive rats. Carotid arterial segments of DOCA, sham (uninephrectomized), or normal (untreated) rats were used for the study. In vitro vasopressin treatment of carotid arteries from normal rats for 24 hours, but not 4 hours, increased both ET-1 and superoxide levels. The increase of vasopressin-induced superoxide was reduced by pretreatment of the vessels with ABT627, a selective ETA receptor antagonist ABT627. Vasopressin, ET-1, and superoxide levels were significant elevated in carotid arteries of DOCA-salt rats compared with sham controls. The selective V1-vasopressin receptor antagonist (beta-Mercapto-beta, beta-cyclopentamethylenepropiony1, O-Me-Tyr2, Arg8 vasopressin, ME-AVP), decreased superoxide both in vasopressin-treated vessels of normal rats and in vessels of DOCA-salt rats, with a concomitant reduction of ET-1 content. These results suggest that vasopressin increases vascular superoxide levels by stimulating ET-1 formation in mineralocorticoid hypertension, and that V1-vasopressin receptors play an important role in this process.
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PMID:Vasopressin induces vascular superoxide via endothelin-1 in mineralocorticoid hypertension. 1262 76

Endothelin (ET)-1 and ET-2 are potent vasoconstrictor peptides with mitogenic activity. In this study, we investigated roles of ET system in renin-angiotensin system (RAS)-mediated hypertension, using transgenic hypertensive mice (THM) with over-expression of both human renin and angiotensinogen genes. In the first step, it was revealed that expression of ET system was locally enhanced, i.e. increases in cardiac preproET-1 mRNA and renal preproET-2 mRNA in THM, compared with the control (wild type) mice. In the next step, we studied the chronic effects of an ET antagonist (SB209670) on THM. Blood pressure (BP) in THM was significantly higher than that in the normal mice during the investigation. However, in the later phase of the study, from 12 to 20 weeks of treatment, THM receiving SB 209670 showed significantly lower BP than that in THM receiving saline. SB 209670 treatment for 20 weeks significantly attenuated phenotypes of cardiac hypertrophy, vascular wall thickening and hypertensive nephropathy observed in THM, suggesting that the ETA/B receptor antagonist is also effective even in the extraordinarily activated RAS condition. These findings suggest that organ specifically activated ET system in THM develops the phenotypes, hypertension, cardiac hypertrophy, and hypertensive nephropathy.
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PMID:The endothelin receptor antagonist ameliorates the hypertensive phenotypes of transgenic hypertensive mice with renin-angiotensin genes and discloses roles of organ specific activation of endothelin system in transgenic mice. 1468 51