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)

Renal prostaglandins (PG) appear to mediate renin release due to stimulation of the intrarenal baroreceptor, but not that due to activation of the macula densa. However, as the role of PG in sympathetically mediated renin release remains unclear, a possible interrelationship between these factors was examined in conscious rats. Hydralazine increased the serum renin levels from 3.1+/-0.8 to 16.7+/-3.0 ng/ml per h at a dose of 1 mg/kg. Indomethacin (5 mg/kg) suppressed urinary PGE(2) and PGF(2alpha) excretion by 89 and 74%, respectively, arachidonate hypotension by 82%, and inhibited the elevated renin levels from hydralazine by 100% without altering the hypotensive effect of the drug. Another PG synthetase inhibitor, meclofenamate, was also effective in attenuating hydralazine-induced renin release, urinary PGE(2) and PGF(2alpha) excretion, and arachidonate hypotension. Isoproterenol, a nonselective beta-adrenergic agonist, increased heart rate, lowered blood pressure, and also stimulated the release of renin when administered intraperitoneally. However, intrarenal infusion of the drug only resulted in increased renin release. Indomethacin inhibited isoproterenol-induced renin release by 66 and 67%, respectively, without altering the hemodynamic effects associated with the intraperitoneal administration of the drug. The selective beta(1) agonist, H133/22, increased the release of renin and heart rate in a dose-related manner without altering blood pressure. H133/22-induced renin release was inhibited by 80% by indomethacin pretreatment. Finally, intrarenal infusions of dibutyryl cyclic AMP (3 mg/kg per min) increased the serum activity from 4.1+/-0.2 to 20.4+/-3.9 ng/ml per h without altering mean arterial pressure. Indomethacin inhibited this renin response to dibutyryl cyclic AMP by 96%. Thus, renal PG appear to be important mediators of sympathetically stimulated renin release acting as a site distal to the beta-adrenergic receptor.
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PMID:Role of renal prostaglandins in sympathetically mediated renin relase in the rat. 3 56

The diagnosis of Bartter's syndrome was made in a 9-month-old boy investigated for poor weight and height gain. Initial treatment with oral potassium supplements and later spironolactone had little or no effect on his growth, although plasma potassium rose to normal after spironolactone. At 33 months indomethacin therapy was started with dramatic results. His symptoms went and his height and weight accelerated into the normal range. In view of the toxicity of indomethacin it was replaced after 12 months by another prostaglandin synthetase inhibitor, ketoprofen, with a satisfactory result. During the change-over period from indomethacin to ketoprofen the expected deterioration in clinical well-being was observed, accompanied by a rise in urinary prostaglandins and plasma renin activity. Prostaglandin synthetase inhibitors provide the best available treatment for Bartter's syndrome.
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PMID:Treatment of Bartter's syndrome in early childhood with prostaglandin synthetase inhibitors. 41 68

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

We examined the relationship between prostaglandin (PG) production and renin release induced by a nonvasoconstrictor dose of an alpha-agonist, phenylephrine, in anesthetized dogs. Intrarenal infusion of phenylephrine (1 microgram/min) did not affect systemic blood pressure or renal blood flow, but increased the renin secretion rate about twofold. The effect of phenylephrine on renin release was abolished by the intrarenal infusion of the alpha-antagonist phentolamine (50 micrograms/min), but was not affected by the intravenous administration of the PG synthetase inhibitor indomethacin (5 mg/kg). Urine flow and urinary sodium excretion rate were not altered by phenylephrine. These results suggest that a nonvascular and nontubular alpha-adrenoceptor mechanism, which is independent of the renal PG system, may be involved in renin release.
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PMID:Renin release induced by a nonvasoconstrictor dose of phenylephrine is independent of the renal prostaglandin system in anesthetized dogs. 620 Jul 12

The inhibitory action of prostaglandin E1 (PGE1) on the vasoconstrictor response to an electrical stimulation of perivascular sympathetic nerve (VSNS) was examined using the perfused central artery of an isolated rabbit ear. This response to VSNS was depressed with PGE1 (2.0 to 5.0 ng/ml in the perfusate) and was augmented with a PG synthetase inhibitor, indomethacin (1.0 microgram/ml). Angiotensin II (1.0 ng/ml) enhanced the response to VSNS, whereas treatment with PGE1 prevented the enhancing effect of angiotensin II completely. In addition, angiotensin II enhanced the response to a bolus injection of noradrenaline in an almost similar manner to that to VSNS. However, PGE1 (2.0 to 5.0 ng/ml) did not inhibit the enhancing effect of angiotensin II on the noradrenaline response. From these results, it is suggested that there may be remarkable antagonism between PGE and the sympathetic nervous system and/or the renin-angiotensin system in the central artery of the isolated rabbit ear, and that PGE1 probably and more potentially acts at presynaptic sites in perivascular sympathetic nerve endings than at postsynaptic ones.
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PMID:Inhibitory action of prostaglandin E on angiotensin II-induced enhancement of vasoconstrictor response to sympathetic nerve stimulation. 668 89

In Bartter's syndrome and in other states with ECFV contraction, very high active plasma renin (PRA greater than 78 ng/ml/hr) is associated with an essential absence of prorenin. In patients whose PRA is less than 50 ng/ml/hr, prorenin accumulates significantly. Patients with Bartter's syndrome treated with PG synthetase inhibitors for 1 week respond with a profound drop in renin, together with a rise in prorenin. Thus, in general, highest active renin values coexist with virtually no prorenin, moderately high renins with rising prorenin, and renins "blocked" by PG synthetase inhibitors with highest prorenin levels. Such a reciprocity between prorenin and renin suggests systemic conversion by means of a convertase mechanism apparently susceptible to PG synthetase inhibitors in vivo but not in vitro. It is also possible that these inhibitors suppress in vivo, but not in vitro, renal renin release more than prorenin release, so that the relative level of prorenin increases. This, coupled with decreased conversion to renin, may contribute to the observed elevation of prorenin.
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PMID:Plasma "prorenin"-renin in Bartter's syndrome, cystic fibrosis, and chloride deficiency, and the effect of prostaglandin synthetase inhibition. 678 70

Renal prostaglandins (PG) appear to mediate the release of renin due to activation of the intrarenal baroreceptor and stimulation of the renal sympathetic nerves. Since the vasodilator hydralazine is thought to stimulate renin release by both of these mechanisms, we examined the effect of indomethacin, a PG synthetase inhibitor, on hydralazine-induced renin release. Hydralazine increased the serum renin levels from 3.3 +/- 0.5 to 13.7 +/- 3.1 and 41.9 +/- 2.4 ng/ml/hr at the 1 and 10 mg/kg doses, respectively. Indomethacin inhibited this hydralazine-induced renin release by 100% at the 1 mg/kg dose and 36% at the 10 mg/kg dose even though the hypotensive effect of the drug was unaltered. Indomethacin (5 mg/kg) also suppressed urinary PGE2 excretion by 60% (p < 0.001). The beta-blocker, propranolol, was as effective as indomethacin in attenuating hydralazine-induced renin release. Additionally, propranolol blocked the tachycardia associated with hydralazine and slightly enhanced the hypotensive action of the drug. When indomethacin and propranolol were combined, no further inhibition of hydralazine-induced renin release was observed. Thus, renal PG's appear to be important as mediators of hydralazine-stimulated renin release but no hydralazine-induced vasodilatation.
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PMID:Inhibition of hydralazine-induced renin release by indomethacin in the rat. 700 82