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)

1. The prostaglandin precursor arachidonic acid (C20:4) increases plasma renin activity in the rabbit and rat when it is infused into the renal arteries. 2. The increase in plasma renin activity after C20:4 in rats is not changed by volume expansion. 3. The inhibitor of prostaglandin synthesis indomethacin decreases plasma renin activity in the rabbit. 4. The increase plasma in renin activity after total renal ischaemia is abolished by pretreatment with indomethacin. 5. C20:4 increases dose- and time-dependent renin release from slices of rabbit kidney cortex. 6. Indomethacin or 5,8,11,14-eicosatetraynoic acid pretreatment in vivo, and addition to the incubation medium, reduces basal as well as C20:4-stimulated renin release in vitro. 7. The stimulating effect of C20:4 on renin release is assumed to be caused directly by formation of prostaglandin endoperoxides in the kidney cortex and not by prostaglandins since in vitro a natural prostaglandin endoperoxide (PGG2) and two stable synthetic prostaglandin endoperoxide analogues (EPA I and EPA II) do increase the release of renin, but PGE2 has no effect and PGF2alpha inhibits renin release.
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PMID:Effects of stimulation and inhibition of the renal prostaglandin synthetase system on renin release in vivo and in vitro. 82 72

The mechanism by which renal prostaglandins stimulate renin secretion in vivo is unknown. In this in vitro study we measured the effects of activation of the prostaglandin (PG) system on renin release from slices of rabbit renal cortex. The PG precursor arachidonic acid (C20:4), a natural PG endoperoxide (PGG2), two stable synthetic PG endoperoxide analogues (EPA I and II), PGE2, PGF2alpha, and two different PG synthesis inhibitors [indomethacin and 5,8,11,14-eicosatetraynoic acid (ETA)] were used to evaluate the possibility of a direct action of the cortical PG system on renin secretion. Renin release increased significantly with time after addition of C20:4, PGG2, EPA I, and EPA II to the incubation medium. Stimulation of renin release was se-related for C20:4 in concentrations of 0.6 to 4.5 X 10(-6) M, for EPA I in concentrations of 0.7 to 2.8 X 10(-6) M, and for EPA II in concentrations of 1.4 to 14.0 X 10(-6) M. Indomethacin (10(-4) M) and ETA (10(-4) M) significantly decreased basal renin release as well as the renin release stimulated by C20:4 and EPA I. PGE2(10(-12) to 10(-6) M) had no effect on renin release, whereas PGF2alpha (10(-12) to 10(-6) M) decreased renin release in a dose-dependent manner. These data raise the possibility of a direct action of the renal cortical PG system on renin secretion. The results further indicate that stimulation of renin release by C20:4 may depend more specifically on the action of PG endoperoxides than on the primary prostaglandins.
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PMID:Stimulation of renin release from rabbit renal cortex by arachidonic acid and prostaglandin endoperoxides. 100 Jul 81

DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCI] is a serotonin (5-HT1C/5-HT2) agonist, with potent cardiovascular effects. The purpose of the present studies was to determine the identity and location of the 5-HT receptor subtype(s) mediating the renin and blood pressure responses to DOI. Injection (i.p.) of DOI to conscious male rats elevated plasma renin activity in a dose-dependent manner. The 5-HT1C/5-HT2 antagonist ritanserin completely blocked the DOI-induced increase in plasma renin activity. In order to distinguish the 5-HT2- from the 5-HT1C- mediated effect of DOI, spiperone was administered before DOI. Low doses of spiperone (0.01 and 0.1 mg/kg, s.c.) significantly reduced the renin response to DOI. Because spiperone has a higher affinity for 5-HT2 than 5-HT1C receptors, these data suggest that DOI stimulates renin secretion through 5-HT2 receptors. To separate central from peripheral 5-HT receptors, we injected DOI into rats pretreated with saline or xylamidine, a 5-HT2 antagonist which does not cross the blood-brain barrier. Xylamidine produced a shift to the right and suppression of the maximal effect of DOI on plasma renin activity, suggesting a role for peripheral 5-HT2 receptors in the effect of DOI. On the other hand, i.c.v. administration of DOI, using doses lower than the peripherally effective doses, caused a significant elevation of plasma renin activity at 200 micrograms/kg. These experiments suggest that DOI's elevation of plasma renin activity has both peripheral and central sites of action.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence that the serotonin agonist, DOI, increases renin secretion and blood pressure through both central and peripheral 5-HT2 receptors. 192 Jan 35

This study examined the role of cGMP in the control of renin release from isolated rat glomeruli. An inverse correlation between renin release and cGMP content of isolated glomeruli was found under several conditions of incubation. Thus, incubation of isolated glomeruli in Ca2+-free media containing EGTA, or the addition of the Ca2+ and calmodulin (CaM) antagonists trifluoperazine (TFP), N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide hydrochloride (W-7), or (8-N, N-diethylamino)-octyl 3,4,5-trimethoxybenzoate-HCI (TMB-8) to glomeruli incubated in Ca2+ replete buffer lowers cGMP and stimulates renin release. These same incubation conditions enhance the release of renin induced by isoproterenol (DBcAMP) in isolated glomeruli. By contrast, raising media K+ to 60 mmol/L, or the incubation of glomeruli with angiotensin II (A-II) or ouabain--all of which are thought to increase intracellular Ca2+--increased glomerular cGMP and suppressed basal glomerular renin release and the increases in renin release induced by isoproterenol (DBcAMP). However, neither exogenous DBcAMP nor nitroprusside, an agent that increased the endogenous cGMP, content of glomeruli mimicked the suppressive effects of high K+, A-II, or ouabain on renin release. Moreover, DBcGMP and nitroprusside also failed to reverse the stimulatory effects of Ca2+ deprivation, TFP, W-7, or TMB-8 on glomerular renin release, even though nitroprusside clearly enhanced cGMP under these conditions of incubation. The results suggest that changes in glomerular cGMP and renin release occur concomitantly in response to alterations in glomerular Ca2+ homeostasis, but that cGMP does not mediate the changes in glomerular renin release.
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PMID:Ca2+-dependent modulation of renin release from isolated glomeruli: apparent independence from alterations in cGMP. 240 29

Fourteen male patients with mild essential hypertension were put on a mackerel and herring diet within a prescribed isocaloric regimen in a cross-over design for 2 weeks. After mackerel diet eicosapentaenoic acid (EPA-C20:5, n-3) appeared more in cholesterol esters (1.7-11.0%), whereas docosahexaenoic acid (DHA-C22:6, n-3) was predominantly incorporated into serum triglycerides (1.0-8.3%). After herring diet, which contained half as much EPA and DHA, their increase was of minor degree. After mackerel diet serum triglycerides, total cholesterol, LDL cholesterol and lecithin cholesterol acyl transferase (LCAT) activity were significantly decreased (by 28%, 9%, 14% and 14%, respectively), returning to the initial levels 3 months later. On the contrary, HDL cholesterol appeared significantly increased (by 12%). After herring diet the differences were not significant. Serum sodium was significantly lower (by 2%) at the end of the mackerel diet as compared to the initial values. On the other hand, uric acid in serum appeared transiently increased (by 24%) at the end of both dietary periods. A significant decrease (by 8%) in casual systolic blood pressure, measured in recumbent position, could be observed only at the end of the mackerel period. Moreover, the level of systolic and diastolic blood pressure before and during a standardized psychophysiological stress test was significantly lower after mackerel diet. Nevertheless, the increments after stress were similar. Plasma renin activity was increased (by 64%) after mackerel diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Blood pressure- and lipid-lowering effect of mackerel and herring diet in patients with mild essential hypertension. 300 Mar 95

Nephrotoxicity is the main untoward effect of cyclosporine (CsA) treatment. Experimental and clinical data suggest that dietary supplementation with fish oil may lessen cyclosporine nephrotoxicity, possibly by lowering renal thromboxane (Tx) production. We have studied the renal effects of a daily supplementation for 2 months of 12 g fish oil (18% C20:5 n-3 eicosapentaenoic acid [EPA] and 12% C22:6 n-3 docosahexanoic acid [DHA]) in a placebo-controlled (12 g corn oil), prospective, randomized, double-blind study of stable CsA-treated liver transplant recipients. Thirteen patients ingested corn oil capsules and 13 fish oil. Compliance with dietary regimen was confirmed by fatty acid chromatography that showed increased plasma concentrations of EPA (from 0.4 +/- 0.02% to 4.6 +/- 0.5%, P < .0001) and DHA (from 1.8 +/- 0.2% to 3.9 +/- 0.1%, P < .0001) in the fish oil group and increased plasma concentration of linoleic acid (C18:2 n-6) in the corn oil group (from 25 +/- 2% to 28.4 +/- 2%, P < .001). At the end of the 2 months of the study, in the fish oil group the effective renal plasma flow increased by 22% (P = .012), the glomerular filtration rate increased by 33% (P = .057), the renal blood flow increased by 17% (P = .024), and the calculated total renal vascular resistances decreased by 20% (P = .034). In contrast, none of these parameters changed in the corn oil group. The renal functional reserve determined during L-arginine infusion, plasma renin activity (PRA), and plasma aldosterone (PA) remained unchanged during the study in either group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal effects of dietary supplementation with fish oil in cyclosporine-treated liver transplant recipients. 748 76

The treatment of renal failure in cirrhotic patients with ascites remains unsatisfactory. Recent studies have shown that the dietary supplementation with fish oil improves the renal function of normal subjects, as well as that of patients with renal failure of different etiologies. We have investigated the renal effects of a daily supplementation for 1 month of 12 g fish oil (27% C20:5 n-3 eicosapentanoic acid [EPA], and 23% C22:6 n-3 docosahexanoic acid [DHA]) in a prospective study of cirrhotic patients with ascites, nine with normal renal function (group 1) and eight with renal failure (glomerular filtration rate [GFR] < 60 mL/min, group 2). Compliance with the dietary regimen was confirmed by fatty acid chromatography that showed increased plasma concentration of EPA (from 1.5 +/- 0.7% to 3.7 +/- 0.8%, P = .024, in group 1; and from 0.53 +/- 0.3% to 2.9 +/- 0.8%, P = .03, in group 2) and of DHA (from 2.1 +/- 0.4% to 3.4 +/- 0.3%, P = .008, in group 1; and from 1.45 +/- 0.5% to 3.8 +/- 0.4%, P = .05, in group 2). At the end of the study, in patients from group 1, the glomerular filtration rate increased by 19% (from 94 +/- 8 to 113 +/- 13 mL/min, P = .039), and the urine flow increased by 39% (from 0.85 +/- 0.14 to 1.12 +/- 0.2 mL/min, P = .039), while no changes occurred in the renal function of patients from group 2. No changes were observed in the urinary excretion of prostaglandin (PG) E2 or of 6-keto prostaglandin-1-alpha (6-K-PGF1-alpha) nor in plasma renin activity (PRA) or the plasma concentration of aldosterone (PA) or antidiuretic hormone (ADH) in both groups. As far as undesirable effects of fish oils were considered, the mean arterial pressure (MAP) decreased in both groups (group 1: from 88.6 +/- 2 to 85.3 +/- 2 mm Hg, P = .015; group 2: from 88.2 +/- 3 to 82.8 +/- 3 mm Hg, P = .05), and bleeding time displayed a significant increase when patients were considered collectively (from 744 +/- 89 to 872 +/- 106 seconds, P = .0068). In conclusion, the administration of fish oil for 1 month was unable to improve renal function in cirrhotic patients with ascites and renal failure. The occurrence of undesirable effects, such as the reduction of arterial pressure and the prolongation of bleeding time, argues against the use of fish oils in these patients.
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PMID:Lack of renal effects of fish oil administration in patients with advanced cirrhosis and impaired glomerular filtration. 902 40

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in tissue remodeling processes. TIMP-1 is the main native inhibitor of MMPs and it contributes to the development of tissue fibrosis. It is known that ANG II plays a fundamental role in vascular remodeling. In this study, we investigated whether ANG II modulates TIMP-1 expression in rat aortic smooth muscle cells. In vitro, ANG II induces TIMP-1 mRNA expression in a dose-dependent manner. The maximal increase in TIMP-1 expression was present after 3 h of ANG II stimulation. The ANG II increase in TIMP-1 expression was mediated by the ANG type 1 receptors because it was blocked by losartan. The increase in TIMP-1 expression was present after the first ANG II treatment, whereas repeated treatments (3 and 5 times) did not modify TIMP-1 expression. In vivo, exogenous ANG II was administered to Sprague-Dawley rats (200 ng. kg(-1). min(-1) sc) for 6 and 25 days. Control rats received physiological saline. After treatment, systolic blood pressure was significantly higher (P < 0.01), whereas plasma renin activity was suppressed (P < 0.01), in ANG II-treated rats. ANG II increased TIMP-1 expression in the aorta of ANG II-treated rats both at the mRNA (P < 0.05) and protein levels as evaluated by Western blotting (P < 0.05) and/or immunohistochemistry. Neither histological modifications at the vascular wall nor differences in collagen content in the tunica media were present in both the ANG II- and saline-treated groups. Our data demonstrate that ANG II increases TIMP-1 expression in rat aortic smooth muscle cells. In vivo, both short- and long-term chronic ANG II treatments increase TIMP-1 expression in the rat aorta. TIMP-1 induction by ANG II in aortic smooth muscle cells occurs in the absence of histological changes at the vascular wall.
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PMID:ANG II increases TIMP-1 expression in rat aortic smooth muscle cells in vivo. 1238 55

The nursing rat pup exposed to hypoxia from birth exhibits ACTH-independent increases in corticosterone and renin/ANG II-independent increases in aldosterone. These increases are accompanied by significant elevation of plasma lipid concentrations in the hypoxic neonates. The purpose of the present study was to compare changes in the concentrations of specific fatty acid metabolites and lipid classes in serum and adrenal tissue from normoxic and hypoxic rat pups. We hypothesized that lipid alterations resulting from hypoxia may partly explain increases in steroidogenesis. Rats were exposed to normoxia or hypoxia from birth, and pooled serum and adrenal tissue from 7-day-old pups were subjected to metabolomic analyses. Hypoxia resulted in specific and significant changes in a number of fatty acid metabolites in both serum and the adrenal. Hypoxia increased the concentrations of oleic (18:1 n-9), eicosapentaenoic (EPA; 20:5 n-3), and arachidonic (20:4 n-6) acids in the triacylglyceride fraction of serum and decreased oleic and EPA concentrations in the cholesterol ester fraction. In the adrenal, hypoxia caused an increase in several n-6 fatty acids in the triacylglyceride fraction, including linoleic (18:2 n-6) and arachidonic acid. There was also an increase in the concentration of alpha-linolenic acid (18:3 n-3) in the triacylglyceride fraction of the hypoxic adrenal, along with an increase in linoleic acid concentration in the diacylglyceride fraction. We propose that specific changes in lipid metabolism in the adrenal, as a result of hypoxia, may partly explain the increased steroidogenesis previously observed. The mechanism responsible may involve alterations in cellular signaling and/or mitochondrial function. These cellular changes may be a mechanism by which the neonate can increase circulating adrenal steroids necessary for survival, therefore bypassing a relative insensitivity to normal stimuli.
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PMID:Metabolomic analysis of adrenal lipids during hypoxia in the neonatal rat: implications in steroidogenesis. 1470 19

Aortic stenosis (AS) results in myocyte and extracellular matrix remodeling in the human left ventricle (LV). The myocardial renin-angiotensin system is activated and collagens I and III and fibronectin accumulate. We determined the yet unknown regulation of enzymes that control collagen turnover, i.e., LV matrix metalloproteinases (MMP) and their tissue inhibitors (TIMPs) in human AS. We compared LV samples from AS patients undergoing elective aortic valve replacement (n=19) with nonused donor hearts with normal LV function (controls, n=12). MMP-2, MMP-9, MT1-MMP, and extracellular matrix metalloproteinase inducer (EMMPRIN), TIMP-1, TIMP-2, TIMP-3, and TIMP-4 mRNA were quantitated by real-time RCR. MMP-1, MMP-2, MMP-3, TIMP-3, TIMP-4, and EMMPRIN protein were measured by immunoblotting and MMP-9 and TIMP-1 protein by ELISA. Gelatinolytic MMP-2 and MMP-9 activity was measured by zymography. MMP-2 was increased in AS at mRNA, protein, and activity levels (131%, 193%, and 138% of controls). MMP-3 protein (308%) and EMMPRIN mRNA and protein were also upregulated (171% and 200%). In contrast, MMP-1 (37%) and MMP-9 mRNA, protein, and activity (26%, 21%, and 52%) were downregulated. MMP-9 activity was inversely correlated with LV size. TIMP-1 mRNA and protein were decreased (55% and 73%). In contrast, TIMP-2 mRNA (358%), TIMP-3 mRNA and protein (145% and 249%) were increased. TIMP-4 mRNA was not altered, but TIMP-4 protein was upregulated to 350%. Changes were similar in AS patients with normal and impaired LV ejection fraction. The dysregulation of myocardial MMPs and TIMPs in human AS starts at an early disease stage when LV function is still normal. In spite of upregulation of some MMPs the balance between MMP and TIMP is shifted towards MMP inhibition in human AS and may contribute to collagen accumulation.
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PMID:Regulation of matrix metalloproteinases and their inhibitors in the left ventricular myocardium of patients with aortic stenosis. 1555 Nov 7


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