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)

This study was undertaken to examine the regulation of renin release and gene expression in primary cultures of juxtaglomerular granular (JGG) cells. JGG cells, isolated from mouse kidney, demonstrated high purity and showed regulated renin release in vitro. Changes in steady-state renin mRNA levels were assessed by quantitative polymerase chain reaction techniques, with polymerase chain reaction amplification efficiency monitored by co-amplification of experimental samples with a dilution series of cDNA for a mutant template. When the cells were incubated in the presence or absence of forskolin, isoproterenol, or 8-bromo-cAMP plus 3-isobutyl-1-methylxanthine for 24 h or cholera toxin for 12 h, renin mRNA levels were increased 3.9-, 4.4-, 5.1-, and 3.3-fold, respectively (all, p < 0.05). A significant increase in renin mRNA levels was observed 8 h after treatment with forskolin, but no change was detectable at 4 h. Cycloheximide did not prevent the increase in renin mRNA by isoproterenol. When RNA synthesis was inhibited by incubation with actinomycin D (5 micrograms/ml), renin mRNA levels declined with a half-life of 3.0 +/- 0.8 h. Treatment with forskolin increased renin mRNA half-life to 10.8 +/- 2.7 h (p < 0.025). The half-life of beta-actin, endothelin-1, or the facilitative glucose transporter-1 (GLUT-1) mRNA expressed in the same cells was not altered, although the steady-state levels of GLUT-1 mRNA increased 2.2-fold after treatment with forskolin. These data demonstrate that cAMP increases renin release and mRNA levels in JGG cells in vitro, that the stimulatory effect of cAMP on renin mRNA is delayed but does not require new protein synthesis, and that the increased renin mRNA levels induced by cAMP are due in part to a selective increase in renin mRNA stability.
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PMID:Cyclic AMP selectively increases renin mRNA stability in cultured juxtaglomerular granular cells. 822 60

Infusion of endothelin-1 (ET-1) (2000 pmol/h) into conscious sheep for 6 days caused a sustained increase in mean arterial pressure (MAP) of 19 +/- 1 mm Hg. This response was mediated by the vasoconstrictor effect of ET-1 and was accompanied by a fall in cardiac output. Plasma renin concentration fell throughout the infusion and atrial natriuretic peptide was increased on day 1 of ET-1 infusion. Hematocrit dramatically increased, probably mainly due to plasma loss resulting from the ET-1-induced increased capillary hydrostatic pressure. To determine whether increased pressor responsiveness to ET-1 played a role in the rise in MAP caused by corticotropin (ACTH), the responses to bolus doses of ET-1 were evaluated before ACTH and on days 3 and 5 of ACTH infusion (5 micrograms/kg/day). ACTH increased MAP from 71 +/- 2 to 87 +/- 3 mm Hg. On the control day ET-1 (400, 1200, and 2000 pmol) increased MAP by 5 +/- 1, 18 +/- 6 and 35 +/- 11 mm Hg, respectively. No initial vasodilation occurred. The responses to all doses of ET-1 were similar during ACTH infusion. Plasma levels of ET-1 did not increase during ACTH infusion. These results demonstrate that long-term infusion of ET-1 caused a sustained increase in blood pressure. There was no evidence that the sensitivity or responsiveness to ET-1 were altered during infusion of ACTH. In conclusion, ET-1 could play a role in the pathogenesis of hypertension but does not appear to be involved in the increase in blood pressure caused by ACTH.
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PMID:Cardiovascular effects of long-term endothelin infusion and responses to endothelin during ACTH infusion in conscious sheep. 826 39

The vasoactive peptide hormones, such as endothelin, renin-angiotensin, and endothelium-derived relaxing factor, have traditionally been viewed as an endocrine system. Recent data demonstrate that their genes and their products are expressed at many local tissue sites. The concept that multiple tissues synthesis peptides has changed out understanding of the physiology of peptide hormone, and this indicated that the autocrine and paracrine system may be important in the regulation of local tissue functions in addition to the circulation endocrine system. Patients with congestive heart failure had markedly higher circulating endothelin-1 level than normal subjects, associated with an activated renin-angiotensin system. Endothelium-dependent vasodilation is attenuated in patients with heart failure. This impaired local vasodilation may contribute to abnormalities in vasoconstriction that are characteristic of heart failure.
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PMID:[Hormonal regulation in cardiac function--endocrine, paracrine, autocrine]. 833 83

The effect of synthetic alpha-human atrial natriuretic peptide (alpha-hANP) on plasma endothelin-1 (ET-1) level was examined in 6 healthy subjects. Intravenous infusion of alpha-ANP (0.1 micrograms/kg/min) resulted in significant falls in plasma renin activity and aldosterone, but without effect on ET-1 level. An angiotensin converting enzyme inhibitor, captopril, increased plasma renin activity and decreased aldosterone, respectively. However, plasma ET-1 levels were not modified by captopril. In cases with alpha-hANP infusion after captopril (25 mg, p.o.,), the renin-angiotensin-aldosterone system was further inhibited compared with the first group, and ET-1 at 60 min was significantly suppressed from the baseline. These data suggest that alpha-hANP when combined with captopril brings about the suppression of plasma ET-1 concentrations in men.
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PMID:Suppression of plasma endothelin-1 level by alpha-human atrial natriuretic peptide and angiotensin converting enzyme inhibition in normal men. 836 64

This study was designed to determine plasma endothelin-1 levels in patients with essential hypertension and diabetes mellitus. Endothelin immunoreactivity was measured in normal controls (n = 30), mild-moderate essential hypertensives (n = 25), Type II diabetic normotensives (n = 25) and hypertensive patients (n = 20). In addition, in ten patients of each group we investigated the relationships of endothelin with other vasoactive hormones. Plasma endothelin concentrations were similar in healthy controls, in essential hypertensives and in diabetic patients with or without hypertension, averaging 8.23 +/- 1.68 pg/ml, 7.7 +/- 1.1 pg/ml, 5.05 +/- 0.94 pg/ml, 7.88 +/- 1.41 pg/ml, respectively. No correlations were observed between endothelin and concentrations of plasma renin activity, aldosterone, catecholamines, atrial natriuretic peptide and arginine-vasopressin. The present study suggests that Type II diabetic patients with or without essential hypertension do not have demonstrably higher values of plasma endothelin than essential hypertensives or healthy subjects.
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PMID:Plasma endothelin in essential hypertension and diabetes mellitus. 841 Sep 22

The peptide vasoconstrictors angiotensin II and endothelin-1, originally described as being derived exclusively from the plasma renin-angiotensin system and vascular endothelium, respectively, have been demonstrated to be produced independently of these sources. Local tissue angiotensin-generating systems are well documented and endothelin production has been demonstrated for a variety of nonendothelial cells, including vascular smooth muscle cells. There is increasing evidence that these locally produced vasoconstrictor peptides may contribute to blood vessel homeostasis, as well as the development of vascular pathologic conditions. Results obtained from pharmaceutical intervention in humans and animals of these systems strongly support this hypothesis. In addition to their vasoconstrictor properties, angiotensin II and endothelin-1 act as potent biologic effectors. In vitro, both vasoconstrictor peptides appear to modulate the activity of autocrine feedback loops in vascular smooth muscle cells. The activity of these feedback loops in vivo may represent a central mechanism for regulation and phenotypic differentiation of this cell type. The most well-established autocrine feedback loops of vascular smooth muscle cells are constituted by platelet-derived growth factor and transforming growth factor-beta, both of which are influenced by the action of angiotensin II and endothelin-1. The effects of the peptide vasoconstrictors on the (auto-) regulated feedback loops are of long-term structural importance, since both vasoconstrictors (via autocrine growth modulators) may influence the composition of the extracellular matrix of vascular smooth muscle cells. This includes effects on the synthesis and secretion of thrombospondin, fibronectin, tenascin, etc. The secretion of extracellular matrix glycoproteins themselves and incorporation into extracellular matrix in vitro appear to be linked to the activity of the autocrine feedback loops: e.g., stimulation of thrombospondin mRNA results in secretion of the glycoprotein only in the concomitant presence of exogenous platelet-derived growth factor, whereas the expression of fibronectin and tenascin may be directed by transforming growth factor-beta. The influence of angiotensin II and endothelin-1 on vascular smooth muscle cell surface receptor expression may represent a secondary mode of action of these vasoconstrictor peptides. Endothelin-1, for instance, can rapidly down-regulate platelet-derived growth factor-alpha receptor mRNA and both angiotensin II and endothelin-1, via induction of transforming growth factor-beta, may interrupt the platelet-derived growth factor based autocrine feedback loop. In vivo, the highly complex interactions between local and systemic vasoconstrictor production, autoregulated feedback loops, and extracellular matrix (which also serves as a reservoir for growth and differentiation modulators) are central to vessel homeostasis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of peptide vasoconstrictors on vessel structure. 848 51

An enzyme which catalyzes the conversion of proendothelin-1 to the potent vasoconstrictor peptide endothelin-1 has been identified in the detergent extract of primary porcine aortic endothelial cell membranes. Partial purification was accomplished by anion exchange and Con A affinity chromatography. The enzyme was active at pH 4 and was inhibited by 100 nM peptstatin A. Hydrolysis products of proendothelin-1 were characterized by bioassay, RIA, HPLC and molecular mass analysis. Comparisons to cathepsin D and renin demonstrated that the endothelin converting enzyme activity from the porcine aortic endothelial cells was unrelated to the known enzymes. These results suggest that the processing of proendothelin-1 by endothelial cells involves a novel pepstatin-sensitive aspartyl protease.
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PMID:Identification of a novel aspartyl endothelin converting enzyme in porcine aortic endothelial cells. 849 May 80

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 present study was designed to analyze quantitatively the effects of a wide range of endothelin-1 levels on renal hemodynamics and renin release in the canine nonfiltering kidney, including their effects on glomerular hydraulic pressure. Intrarenal infusion of endothelin-1 produced dose-dependent reductions in renal blood flow, but it did not affect glomerular hydraulic pressure until the infused dose reached high rates. At the rate of 1.0 ng/kg per minute, endothelin-1 reduced renal blood flow by 23% (p < 0.01), whereas glomerular hydraulic pressure was not significantly changed from 68.1 +/- 1.3 to 67.4 +/- 1.2 mm Hg. However, with a higher rate of endothelin-1 infusion (5.0 and 10.0 ng/kg per minute), glomerular hydraulic pressure fell to 59.5 +/- 1.3 and 51.5 +/- 1.8 mm Hg (p < 0.01), whereas renal blood flow was reduced from 154.5 +/- 15 to 83.0 +/- 9.5 and 53.5 +/- 9.9 mL/min, respectively. Endothelin-1 infusion also produced an inhibitory effect on renin release. With infusion at 1.0 ng/kg per minute, renin release fell from the control level of 47.9 +/- 5.6 to 26.6 +/- 4.9 units/min per gram kidney weight (p < 0.01), and it fell further to 16.1 +/- 4.3 units/min per gram kidney weight with infusion at 10.0 ng/kg per minute. In summary, endothelin-1 infusion did not affect glomerular hydraulic pressure despite a fall in renal blood flow at low doses, but at high doses it reduced both, suggesting that endothelin-1 exerts separate, dose-dependent effects on preglomerular and postglomerular resistances.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of endothelin-1 on glomerular hydraulic pressure and renin release in dogs. 850 Aug 65

The aim of the study was to investigate endothelin-1 (ET-1) and neuropeptide Y (NPY) plasma concentrations in renal venous blood of hypertensive patients with unilateral renal artery stenosis (URAS). The study was performed in 22 patients with URAS and 18 patients diagnosed as essentially hypertensive. In each subject renal arteriography and renal vein catheterisation was performed. Blood samples for ET-1, NPY and plasma renin activity (PRA) were withdrawn from renal veins and vena cava inferior, and for ET-1 and NPY from the aorta. Patients with URAS were divided in two subgroups according to the renal vein renin ratio. Both in nine patients with URAS and ratio > 1.5 and in 13 patients with URAS and ratio < 1.5, ET-1 and NPY plasma concentrations evaluated in renal venous blood of the ischaemic kidney were not different from those assessed in the contralateral side, in vena cava inferior and in the aorta. In essential hypertension, the mean ET-1 and NPY plasma concentrations of both renal veins were not different from the ET-1 and NPY plasma values assessed in renal vein of stenosed and contralateral side, vena cava and aorta of patients with URAS with and without activation of the renin system. Our study indicates that chronic ischaemia does not affect ET-1 and NPY plasma concentrations in renal venous blood of hypertensive URAS patients both with and without activation of the renin system.
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PMID:Endothelin-1 and neuropeptide Y plasma concentrations in renal venous blood of hypertensive patients with unilateral renal artery stenosis. 857 97


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