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)

In a 52-year-old patient with Bartter's syndrome, peripheral venous prostaglandin E2 (PGE2) and plasma renin activity (PRA) levels were markedly elevated and plasma aldosterone concentration (pa) was at the upper limit of normal, though inappropriately high relative to the decreased plasma and whole body potassium levels. Blood pressure, plasma volume, exchangeable body sodium, plasma cortisol and urinary catecholamines were normal. Renal venous PGE2 was two to three times higher than peripheral PGE2. Indomethacin (300 mg/day) decreased peripheral PGE2 by 50%, PRA by 84% and PA by 72%, induced a positive potassium balance (greater than 350 mEq) with normal plasma potassium levels, and returned the previously marked resistance to the pressor effect of angiotensin II to normal. During the entire study, highly significant correlations (p less than 0.001) between peripheral PGE2 and PRA (r = 0.86) or PA (r = 0.90) were found. In this patient the hyperreninemia was not related to volume depletion. These data indicate that in Bartter's syndrome renal PGE2 secretion may be increased, systemic blood levels of PGE2 may be elevated and closely related to PRA, and indomethacin ameliorates these abnormalities and improves potassium balance. These results are consistent with the ascription of an important role to excessive renal PGE2 secretion in the pathogenesis of Bartter's syndrome.
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PMID:[Increased renal prostaglandin E2 secretion in Bartter's syndrome]. 92 54

125Iothalamate and 131I-hippuran clearances, sodium excretion and plasma renin activity (PRA) before and during indomethacin administration in an oral dose of 3 x 50 mg/day were studied in volunteers with a normal or reduced kidney function, as well on non-sodium-restricted as on sodium-restricted diet. Indomethacin induced a temporary sodium and water retention and a decrease in glomerular filtration rate. It also lowered PRA. The latter phenomenon did not depend on sodium retention and was present within 2 h after an oral dose of 50 mg. The results may be explained by indomethacin-induced inhibition of prostaglandin synthesis.
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PMID:The effect of indomethacin on kidney function and plasma renin activity in man. 95 Oct 14

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

1. Indomethacin inhibits prostaglandin synthesis and interferes with renin release; these effects were studied in rabbit renovascular hypertension. 2. Ten intravenous injections (3 mg day-1 kg-1 after two initial doses of 9 mg/kg) of indomethacin were given daily to ten normal rabbits, ten rabbits with two-kidney Goldblatt hypertension (2KH), tension (1KH). Twelve appropriate control rabbits received diluent phosphate buffer without indomethacin. Plasma renin activity and plasma prostaglandin E2 were measured by radioimmunoassay. 3. In the normal group, indomethacin significantly decreased plasma prostaglandin E2 (1-15 to 0-2 ng/ml, SEM 0-2; P less than 0-01) and plasma renin activity (20 to 3 ng h-1 ml-1, SEM 1, P less than 0-01). Plasma creatinine increased slightly but the mean blood pressure was not significantly changed by indomethacin. 4. Six of ten rabbits with 2KH showed results similar to those in the normal rabbits. In four of ten rabbits in which development of 2KH was accompanied by increments in plasma renin activity (18 to 31-5 ng h-1 ml-1, SEM 3 and 4 respectively; P less than 0-01) and plasma prostaglandin E2 (1-2 to 3-4 ng/ml, SEM 0-2 and 0-4 respectively; P less than 0-05), treatment with indomethacin produced renal failure (plasma creatinine increasing to 7-6 mg/100 ml), oliguria, malignant hypertension (mean blood pressure, 168 mmHg, SEM 7-7) and death within 5 days. 5. In 1KH, indomethacin decreased plasma renin activity and plasma prostaglandin E2, but caused increased mean blood pressure (102 to 121 mmHg, SEM 4 and 6 respectively; P less than 0-01) and decreased renal function (plasma creatinine 0-9 +/- 0-04 to 3-5 +/- 1 mg/100 ml, SEM 0-04 and 1 respectively; P less than 0-01). 6. Aggravation of hypertension was conditioned by pre-existing levels of renal function and, to a lesser extent, by plasma renin activities. 7. These results suggest that prostaglandins exert a protective effect on renal function in renovascular hypertension.
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PMID:Effects of indomethacin in rabbit renovascular hypertension. 107 20

1. Inhibition of prostaglandin synthesis by indomethacin induced an increase in blood pressure which did not occur when rats were bilaterally nephrectomized. 2. The blood pressure effect was related to the state of sodium balance and thus to the activity of the renin--angiotensin system. 3. Indomethacin induced a decrease in renal blood flow. 4. Angiotensin receptor blockade with Sar1-Ala8-angiotensin II blunted the blood pressure effect and prevented the renal haemodynamic changes induced by indomethacin.
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PMID:Effect of a competitive angiotensin antagonist on the renal haemodynamic changes induced by inhibition of prostaglandin synthesis in rats. 107 81

1) The influence of oral indomethacin on basal and stimulated plasma renin activity in normal human subjects was determined. 2) Indomethacin lowers the basal plasma renin activity in man. 3) The response of the plasma renin activity after indomethacin to physiological and pharmacological stimuli is maintained at a lower level. 4) There is no evidence from our experiments that major changes in the sodium balance are responsible for the effects observed.
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PMID:The effect of indomethacin on plasma renin activity in man under normal conditions and after stimulation of the renin angiotensin system. 110 96

The influence of indomethacin, a potent inhibitor of prostaglandin synthesis, on basal and stimulated plasma renin activities in normal human subjects was determined. Stimulation of the renin activity was achieved by orthostasis or by furosemide. Indomethacin led to a considerable decrease of both basal and stimulated plasma renin activity in chronic and acute experiments. Our experiments provide no evidence that major changes in the sodium balance are responsible for the effects observed. It is concluded that some antagonistic function of the renin angiotensin system and prostaglandins seems probable. These antagonistic actions might play a role in the regulation of the kidney circulation or the arterial blood pressure.
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PMID:[The effect of indomethacin on basal and stimulated plasma renin activity in normal subjects (author's transl)]. 126 2

The rat remnant kidney model, produced by approximately five-sixths reduction in functional renal mass, is characterized by renal vasodilation, impaired autoregulation, and increased activity of the renin-angiotensin system. The present studies were designed to investigate the role of vasodilatory prostaglandins (PGs) in the altered hemodynamics in the remnant kidney. Four weeks post-ablation, renal blood flow (RBF), was significantly higher in rats fed a standard protein (SP) diet (n = 16) compared with low-protein-fed (LP) rats (n = 7) (6.2 +/- 0.6 vs. 3.7 +/- 0.5 ml/min; P < 0.01), autoregulation was impaired in SP rats [autoregulation index (AI) 1.0 +/- 0.1 (SP) vs. 0.2 +/- 0.1 (LP); P < 0.05], and renin secretory rates were significantly increased in SP rats both during the basal state [24 +/- 7 (SP) vs. 2 +/- 1 (LP) ng.ml-1 x h-1 x min-1; P < 0.05] and after reduction in renal perfusion pressure [110 +/- 29 (SP) vs. 16 +/- 7 (LP); P < 0.05]. Indomethacin administration (5 mg/kg bolus + 5 mg.kg-1 x h-1 infusion) in additional SP rats (n = 11) decreased RBF from 7.4 +/- 1.1 to 5.9 +/- 1.0 ml/min (P < 0.05) without improvement in autoregulation (AI = 1.1 +/- 0.3). Renin basal secretory rate and response to decreased renal perfusion pressure were not altered by indomethacin. These data suggest that PGs contribute to the renal vasodilation in the rat remnant kidney model, but they do not mediate the impaired renal autoregulation or the increased renin release.
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PMID:Prostaglandins do not mediate impaired autoregulation or increased renin secretion in remnant rat kidneys. 148 82

The hypothesis that potassium depletion (KD) might play a role in stimulating the renal synthesis of prostanoids, and that these materials can contribute to hypokalaemic renal dysfunction, has been tested. Healthy women were studied either in normal potassium balance (N,n = 14), or in experimental KD. KD was induced by low dietary potassium intake (less than or equal to 10 mmol day-1) and natriuretic treatment, associated with replacement of net NaCl and water loss. By using different depletive patterns, two groups with estimated cumulative potassium deficits of 160 +/- 43 mmol (KD1, n = 8) and 198 +/- 22 mmol (KD2, n = 6), respectively, were obtained. Renal function by the clearance (cl.) method and urinary PGE2, 6-keto-PGF1 alpha, TxB2 concentrations by the RIA method were measured during hypotonic polyuria (oral water load) and subsequent moderate antidiuresis induced by the infusion of low-dose lysine-8-vasopressin (LVP). Compared to the N group, only in the KD2 group do glomerular and tubular dysfunctions typical of hypokalaemia and reduced prostanoid excretions (significant for 6-keto-PGF1 alpha and TxB2 but not for PGE2) appear during polyuria besides the significant reductions of plasma potassium concentration, urinary potassium excretion and the significant increase in plasma renin activity. During LVP infusion the urinary prostanoid excretions were all significantly lower in absence of significant differences in urinary flow rate. Concerning its renal effects, LVP lost its ability to reduce the creatinine cl., while expressing a trend towards reduction in fractional chloride excretion. Indomethacin pretreatment restored the LVP effect on creatinine cl. and increased the antichloruretic LVP effect (although not significantly). To the extent that urinary prostanoid excretions reflect their intrarenal synthesis, our data demonstrate that KD inhibits this biosynthesis. A depressed production of prostanoids endowed with vasodilating and chloruretic activity probably played a role in attenuating the renal vascular hyporeactivity and the urinary chloride dispersion induced by KD.
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PMID:Effects of experimental potassium depletion on renal function and urinary prostanoid excretion in normal women during moderate anti-diuresis. 154 Oct 86

The direct effects of rat endothelin (ET-3) on renal function and prostanoid levels were examined in the isolated, oncotically perfused kidney of the rat. ET-3 at 0.75 and 2.0 ng/ml produced sustained increases in perfusion pressure of 46 and 83 mm Hg, respectively, as compared with control kidneys. Glomerular filtration rate was significantly higher than control after additions of ET-3 as was the absolute and fractional excretion of water and electrolytes. ET-3 increased perfusate 6-keto-prostaglandin (PG)F1 alpha (breakdown product of PGI2) levels and stimulated greater urinary excretion of PGE2 and PGF2 alpha than 6-keto-PGF1 alpha. ET-3 did not affect urinary excretion or perfusate levels of thromboxane B2. Time-dependent increases in renin release were suppressed by ET-3. Indomethacin (10 microM) prevented ET-3-induced increases in urinary and perfusate prostanoids; however, renal vasoconstrictor and excretory responses were the same in the presence or absence of indomethacin. These results indicate that ET-3 acts directly on the perfused rat kidney to increase the release of prostanoids from the vascular and urinary compartments. A modulatory influence of prostaglandins on the acute renal hemodynamic and excretory effects of ET-3 was not observed under these conditions.
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PMID:Endothelin-3 effects on renal function and prostanoid release in the rat isolated kidney. 162 3


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