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)

Although the PGs operate mainly in the renal medulla the demonstration of PG biosynthesis in the renal cortex has provided a biochemical basis for a direct relationship between the PGs and the renin-angiotensin system. The formation of PGs is influenced by circulating levels of A I probably by indirect mechanisms. That the release of renin at least under certain experimental conditions is dependent on the PG system is suggested by the following findings: 1. C20:4 increases PRA in the rabbit and rat. 2. Indomethacin decreases PRA in the rabbit. 3. C20:4 stimulates renin release from slices of rabbit kidney cortex. 4. Reduced renal perfusion pressure and ischemia are accompanied by release of both PGs and renin. 5. The release of PG and renin following renal ischemia is blocked by treatment with indomethacin. The actions of the renin-angiotensin system and the renal PGs are, as far as we know them, antagonistic to each other. PGEs are vasodilator, increase renal blood flow, inhibit adrenergic neurotransmission, and cause excretion of electrolytes and water. Conversely, A II is vasoconstrictor, decreases renal blood flow, stimulates adrenergic neurotransmission, and conserves water and electrolytes. Thus, the interaction between the renal PGs and renin seems to be one in which the two hormonal systems stimulate each other's formation or release, but opposes each other's actions. Further studies are necessary to reconcile this apparent contradiction.
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PMID:Interactions between the renal prostaglandins and the renin--angiotensin system. 79 Sep 16

The effect of indomethacin or placebo on aldosterone, plasma renin activity (PRA), sodium excretion, and urinary prostaglandin (PG) levels was investigated in five hypertensive subjects in 100 mEq sodium balance who had experienced malignant hypertension with a disturbance of their renin-aldosterone relationship in the past. Indomethacin significantly lowered aldosterone levels by 43%, PRA by 58%, 24-hour sodium excretion by 49%, and urinary PG excretion, an indicator of renal PG synthesis, by 67%. Angiotensin infusion increased aldosterone to the same level before and after treatment with indomethacin. Similarly, in normal subjects in 150 mEq sodium balance, indomethacin lowered PRA by 47%; sodium excretion fell by 33%, and urinary prostaglandin E (PGE) excretion, by 55%. The acute elevation in PRA 10 minutes after intravenous furosemide was completely abolished by indomethacin. Five subjects with essential hypertension were classified as normal renin hypertensives according to their response to orally administered furosemide. Indomethacin pretreatment resulted in 60% reduction of PRA following furosemide, and three of these subjects now fell into the low renin category. Studies in vitro demonstrated that indomethacin has no effect on the renin-renin substrate interaction. Thus, indomethacin lowers PRA concomitantly with a reduction in renal PG synthetase activity. Whether indomethacin inhibits renin release by an intrarenal, PG-related mechanism or secondarily via sodium retention is discussed.
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PMID:Suppression of plasma renin activity by indomethacin in man. 82 75

The effects of furosemide on stimulation of renin secretion and urinary sodium excretion were studied in dogs pretreated with the prostaglandin synthetase inhibitors, indomethacin and meclofenamate. Pretreatment with these drugs failed to modify the natriuretic response to furosemide but completely blocked the rise in arterial plasma renin concentration produced by the diuretic. The organic acid probenecid did not affect either the natriuretic response or the increase in renin. In separate experiments, it was not possible to separate the effects of indomethacin on prostaglandin secretion, the renin-angiotensin system or renal hemodynamics. It is concluded that in the dog the natriuretic response to furosemide is not linked to the possible prostaglandin-induced increase in renal blood flow. Indomethacin apparently affects furosemide-induced renin secretion at both the vascular and macula densa sites. The data also suggest that the prostaglandins may be more important than the renin-angiotensin system in the modulation of intrarenal hemodynamics.
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PMID:Natriuretic effect of furosemide after inhibition of prostaglandin synthetase. 82 42

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

Indomethacin inhibits the synthesis of prostaglandin and the release of renin. These effects were studied in normal rabbits and rabbits with two-kidney Goldblatt hypertension (2KGH) and one-kidney Goldblatt hypertension (1KGH) by giving daily intravenous injections of indomethacin (3mg/kg after two initial doses of 9 mg/kg), and in appropriate control rabbits given diluent phosphate buffer without indomethacin. In normal rabbits, indomethacin significantly decreased immunoreactive plasma prostaglandin E-like substance (IPGE) and plasma renin activity (PRA). Indomethacin did not change plasma creatinine (PCr) or mean blood pressure but it decreased renal blood flow (RBF) and glomerular filtration rate (GFR). In 2KGH rabbits, responses depended on the level of renal function and, to a lesser extent, on the level of PRA. In six of10 2KGH rabbits in which hypertension developed without significant changes in PRA, IPGE, PCr, RBF, and GFR, indomethacin produced changes similar to those seen in normals. In the other four rabbits, development of 2KGH was accompanied by increased PRA, increased IPGE, and decreased RBF and GFR, and indomethacin produced renal failure, oliguria, malignant hypertension, and death within 5 days. In 1KGH rabbits, indomethacin decreased IPGE, PRA, and renal function but increased mean blood pressure. These observations suggest that prostaglandins exert a protective effect on renal function in renovascular hypertension.
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PMID:The effect of indomethacin blockade of prostaglandin synthesis on blood pressure of normal rabbits and rabbits with renovascular hypertension. 83 Apr 37

Arachidonic acid (C20 :4) plasma renin activity (PRA), PGF2alpha, and sodium excretion were determined before and after furosemide in men. C20 : 4 and PRA increase (p less than 0.005) within 10 min after furosemide, PRA then decreased again whereas C20 : 4 levels remained elevated. Maximal exretion of PGF2alpha and sodium occurred 30-60 min after furosemide. Indomethacin prevented the rise of C20 : 4, PRA and PGF2alpha after furosemide, leaving sodium excretion unaltered. The release of C20 : 4 is assumed to be the primary mechanism of furosemide to increase PG biosynthesis and renin release.
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PMID:Increase of free arachidonic acid by furosemide in man as the cause of prostaglandin and renin release. 83 74

Adminstration of endotoxin to dogs caused a rapid initial decline in blood pressure followed by a transient recovery preceding death. Plasma renin activity was elevated 5 minutes after endotoxin administration and continued to rise throughout the course of shock. Indomethacin given 60 minutes after endotoxin caused an elevation of blood pressure and a 50% decrease in plasma renin activity. Pretreatment with indomethacin markedly attenuated both the hemodynamic changes and the rise in plasma renin activity caused by endotoxin administration. Prostaglandin (PG) E-like material was observed in renal venous blood 30 minutes after endotoxin administration and was abolished by indomethacin. In addtion, a non-PG substance was found in dialysate from both arterial and renal venous blood within 5 minutes of endotoxin administration, Renal and mesenteric angiograms were taken at various stages of shock. Endotoxin administration caused a substantial increase in the diameter of intrarenal arterial branches which was temporally associated with the appearance of PGE-like material in the renal venous effluent. The mesenteric arteries were initially and transiently constricted by endotoxin and then were markedly and chronically dilated. Indomethacin simultaneously abolished renal PG and decreased renal and mesenteric arterial diameter.
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PMID:Prostaglandins and the renin-angiotensin system in canine endotoxemia. 85 Jan 31

Potassium deficiency for 3 weeks in dogs caused 374 +/- 38 mEq of sodium retention with increase in body weight, plasma volume, and inulin space. Cardiac output increased from 3.7 +/- 0.6 to 5 +/- 0.6 liters/min (P less than 0.02) and systemic vascular resistance decreased from 3,050 +/- 590 to 2,000 +/- 286 dynes/cm per sec2 (P less than 0.05). Plasma renin activity (PRA) increased from 0.4 +/- 0.1 to 17.2 +/- 0.9 ng/ml per hour (P less than 0.01) without change in plasma aldosterone. Angiotensin sensitivity decreased from a rise of 37 +/- 4 mm Hg in mean arterial pressure (MAP) to 10 ng/kg per min before potassium depletion to a rise of 10 +/- 2 mm Hg after hypokalemia. Urinary prostaglandin E (PGE) excretion increased from control values of 1,224 to 1,556 ng/day to 9,352 +/- 3,670 after 21 days of hypokalemia (P less than 0.01). Indomethacin, 150 mg a day for 3 days, decreased urinary PGE to control values as PRA decreased from 17.2 +/- 5.9 to 1.1 +/- .3 ng/ml per hour and angiotensin sensitivity was partially restored. These findings indicate that hypokalemia increased urinary PGE with extracellular fluid volume expansion, decreased sensitivity to angiotensin and increase in PRA.
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PMID:The hemodynamic effects of potassium deficiency in the dog. 87 Feb 19

The urinary excretions of prostaglandin E-like material (iPGE) and kallikrein were measured in two children with Bartter's syndrome. Urinary iPGE excretion was three and 10 times greater than normal, and urinary kallikrein was five and 10 times greater than normal in the two subjects. Furthermore, excretions of iPGE and kallikrein were highly correlated (P less than 0.005) with each other before and during treatment with indomethacin, a prostaglandin synthetase inhibitor. Indomethacin significantly (P less than 0.001) reduced urinary iPGE, urinary kallikrein, and plasma renin activity, while increasing the sensitivity to intravenous angiotensin II and the serum potassium to normal. The results confirm that renal prostaglandins may be involved in the pathogenesis of Bartter's syndrome and suggest that renal prostaglandins and the kallikrein-kinin system are linked.
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PMID:Bartter's syndrome: urinary prostaglandin E-like material and kallikrein; indomethacin effects. 90 Jun 71

Bartter's syndrome may result from a disturbance of the interrelations of three vasoactive hormonal systems: the kallikrein-kinin, renin-angiotensin, and prostaglandin systems. Although kinin and angiotensin have opposing effects on renal function, each hormone increases the levels of prostaglandins within the kidney. Elevated renal prostaglandin levels are primarily responsible for some of the major features of the syndrome. The effectiveness of indomethacin in the treatment of Bartter's syndrome derives in large part from the ability of the drug to inhibit prostaglandin production. Indomethacin also decreases the activity of the renin-angiotensin system and the excretion of renal kallikrein, perhaps related to inhibition of prostaglandin mechanisms that may participate in the release of renin and kallikrein. However, additional actions of indomethacin must be considered, such as an effect of the drug on a naturally occurring renin inhibitor.
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PMID:Bartter's syndrome results from an imbalance of vasoactive hormones. 90 Jun 81


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