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

Since dietary salt loading enhances nitric oxide (NO) generation in the kidney, we investigated the hypothesis that changes in salt intake have specific effects on vascular resistance in the kidney mediated by the L-arginine-NO pathway. We contrasted changes in renal and hindquarter vascular resistances (RVR and HQVR) in anesthetized rats during intravenous infusions of graded doses of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Groups (N = 8 to 10) of rats were maintained on a high salt (HS) or low salt (LS) diet for two weeks. Compared to those on LS, rats on HS had a greater increase in mean arterial pressure (delta MAP; +32 +/- 4 vs. +22 +/- 3%; P = 0.05) and RVR (+160 +/- 17 vs. +83 +/- 10%; P < 0.005) and a greater fall in renal blood flow (delta RBF; -47 +/- 3 vs. -32 +/- 4%; P < 0.01); changes in HQVR were similar in the two groups. The enhanced RVR response to L-NAME in HS rats could not be ascribed to the higher renal perfusion pressure (RPP) since it persisted in rats whose RPP was controlled by adjustment of a suprarenal aortic clamp. Changes in RVR with an NO donor (SIN-1) were similar in HS and LS rats. L-NAME reduced plasma renin activity in both HS and LS rats. After inhibition of ACE with captopril, or of angiotensin II type I (AT1) receptor with losartan, the increase in RVR with L-NAME remained greater in HS than LS rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal vasoconstriction during inhibition of NO synthase: effects of dietary salt. 752 72

The aim of the present study was to investigate the endothelial influence on renin secretion of isolated juxtaglomerular cells. Specifically the role of nitric oxide (NO) and of endothelin was studied. Coculture of primary cultures of juxtaglomerular cells with aortic and microvascular endothelial cells decreased renin secretion. Inhibition of NO formation by absence of l-arginine or presence of N omega-nitro-l-arginine caused a marked decrease in cGMP accumulation and a reduction in renin secretion in cocultures. Exogenous NO (NO liberators sodium nitroprusside/SIN 1) stimulated the 20-hour renin secretion from juxtaglomerular cells markedly, too. The effect of NO on renin secretion was biphasic: short-time inhibition and long-time stimulation of renin release. NO's stimulatory effect on renin secretion is dependent on extracellular calcium, but independent on cAMP or cGMP accumulation. Endothelin 1, 2, and 3 did not affect basal renin secretion, but inhibited cAMP stimulated renin release to a similar extent. Endothelin's action is not mediated via the subtype A endothelin receptor, but seems to involve calcium mobilization in juxtaglomerular cells that is dependent on extracellular calcium and associated with prominent calcium activated chloride channels. Taken together, coculture of juxtaglomerular cells with endothelial cells inhibits renin secretion despite the stimulatory effect of native NO released from endothelial cells. cAMP stimulated renin secretion is inhibited by all three endothelin isoforms thus contributing to the inhibition of renin secretion in coculture.
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PMID:Endothelium-mediated regulation of renin secretion. 770 11

This study aimed to examine the role of nitric oxide (NO) in the regulation of renin secretion from renal juxtaglomerular (JG) cells. Using primary cultures of mouse renal JG cells, we found that sodium nitroprusside (SNP) and 3-morpholino-sydnonimin-hydrochloride (SIN-1), two structurally different liberators of NO, led to a transient inhibition during the first hour followed by a marked dose-dependent stimulation of renin secretion lasting for an additional 20 h. This stimulatory effect was blunted by methylene blue (50 microM) and was reversible within minutes after removal of the NO liberators. SNP and SIN-1 also stimulated guanylate cyclase activity in the cultures with a maximum within the first hour of incubation. Increasing intracellular guanosine 3',5'-cyclic monophosphate levels by 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (100 microM) or by atrial natriuretic peptide (10 nM) decreased basal renin secretion but did not inhibit the effect of SNP. The stimulatory effect of SNP was not related to adenosine 3',5'-cyclic monophosphate levels in the JG cells and was blunted after chelation of extracellular calcium by 2 mM ethylene glycol-bis(beta-amino-ethyl ether)-N,N,N'N'-tetraacetic acid. Taken together, our findings suggest that liberators of NO have two effects on renin secretion from isolated JG cells: an inhibitory effect mediated by stimulation of soluble guanylate cyclase activity and a stimulatory effect mediated by an as yet unknown pathway that requires extracellular calcium.
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PMID:Liberators of NO exert a dual effect on renin secretion from isolated mouse renal juxtaglomerular cells. 839 40

The aim of the present study was dual: first to establish that a preparation of afferent arterioles freshly isolated from the rat kidney is a suitable model to study renin release and synthesis, and second to investigate the effect(s) of nitric oxide (NO) inhibition on renin release in this model. Purification of renal microvessels was based on iron oxide infusion into the kidneys and separation of the afferent arterioles from glomeruli and connective tissue with a magnet. These microvessels express preprorenin mRNA, contain renin granules and release renin as evidenced by RT-PCR, immunocytochemistry and measurement of renin activity, respectively. Renin secretion was increased in isolated afferent arterioles after in vivo treatment with the diuretic furosemide (+300%) or in vitro treatment with the adenylyl cyclase activator forskolin (+50%), indicating that this vascular preparation responds appropriately to regulators of the renin-angiotensin system. Furthermore, in afferent arterioles isolated from control rats, renin release was positively correlated with total renin content (r = 0.85). In afferent arterioles isolated from rats chronically treated with the NO-synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), forskolin was ineffective in modifying renin release despite stimulation of cAMP levels. In addition, the correlation between renin release and tissue renin content was disrupted. Similar results were obtained when cortical slices were used instead of afferent arterioles, suggesting that this defect in the regulation of renin release is independent of the presence of macula densa cells. To verify that the lack of regulation of renin release after L-NAME treatment was due to NO inhibition, the NO donor 3-morpholino-syndonimin-hydrochloride (SIN-1) was administered in afferent arterioles or cortical slices from kidneys of L-NAME-treated rats. In both preparations, SIN-1 reversed the L-NAME effect and re-established the responsiveness of renin release to forskolin and the relationship between renin release and renin content. These data indicate that the adenylyl cyclase-mediated mechanism regulating renin release is impaired when NO synthesis is inhibited.
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PMID:Regulation of renin release is impaired after nitric oxide inhibition. 864 2

The chronic treatment of rats with N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) biosynthesis, results in hypertension. This inhibition of NO production results in activation of the renin-angiotensin system, with increased activity of the carboxypeptidase angiotensin I-converting enzyme (ACE). Since chronic NO inhibition increases ACE activity, we hypothesized that this inhibition could also affect the activities of other peptidases involved in cardiovascular functions. To test this possibility, we examined the activities of aminopeptidase M (APM), dipeptidyl peptidase IV (DPP IV), metalloendopeptidase 24.15 (MEP 24.15) and neutral endopeptidase 24.11 (NEP 24.11) in rat brain, heart, kidney, liver, lung and thoracic aorta. Male Wistar rats were treated chronically with L-NAME (80mgkg(-1) per day) administered in the drinking water for 4 weeks and their organs then removed and processed for the determination of peptidase activities. Treatment with L-NAME did not significantly alter the activities of the four peptidases in brain, heart, kidney, liver and lung. In contrast, in aorta, the activity of APM was slightly but significantly reduced whereas those of DPP IV and MEP 24.15 were markedly enhanced; NEP 24.11 was not detected in this tissue. Immunoblotting for DPP IV and MEP 24.15 showed increased expression in aortic tissue. Neither L-NAME (1-100microM) nor the NO donors sodium nitroprusside and 3-morpholinosydnonimine (SIN-1; 1-100microM) had any consistent effect on the activity of recombinant MEP 24.15 or renal DPP IV. The importance of MEP 24.15 in peptide metabolism was confirmed in pentobartibal-anesthetized rats pretreated with the MEP 24.15 inhibitor N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Aib-Tyr-p-aminobenzoate (JA2), which significantly potentiated the hypotensive response to bradykinin. The altered peptidase activities seen in aorta may contribute to modulating vascular responses in this model of hypertension.
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PMID:Peptidase activities in rats treated chronically with N(omega)-nitro-L-arginine methyl ester (L-NAME). 1519 92