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)

The present study investigates the antihypertensive action of cicletanine, a new antihypertensive compound with diuretic properties (or placebo), on vasopressor (catecholamines, renin-aldosterone) as well as vasodepressor (prostaglandins, kallikrein-kinin) systems in conscious chronic sinoaortic denervated (SAD) dogs. Cicletanine (10 mg/kg twice a day, per os, for one month) lowered blood pressure and heart rate. The antihypertensive action does not involve an effect on sympathetic tone (since plasma catecholamine levels were unmodified) or on plasma aldosterone levels. By contrast, urinary 6 keto PGF1 or PGE2 levels and kallikrein activity were enhanced. This result indicates that the antihypertensive effect of cicletanine is associated with a stimulation of potential vasodepressor systems (such as prostaglandins or kinins).
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PMID:Effects of cicletanine on vasoactive systems in conscious sinoaortic-denervated dogs. 178 61

The acute effects on urinary electrolyte excretion and plasma potassium were compared of the anti-hypertensive dihydrofuropyridine cicletanine with the thiazide bendrofluazide in 6 patients with uncomplicated essential hypertension. Cicletanine 50 mg or 100 mg and bendrofluazide 5 mg caused no acute decrease in blood pressure compared to placebo for 24 h after treatment. In the 24 h after a single dose of cicletanine 50 mg there was no increase in urinary sodium, potassium or volume compared to placebo. After a single dose of cicletanine 100 mg there was a significant increase in 2 h urinary sodium excretion compared to cicletanine 50 mg and in the first 6 h a significant increase in urinary potassium compared to placebo. Urine volume did not change significantly. After bendrofluazide 5 mg urinary sodium excretion increased significantly in the first 6 h as well as in the subsequent 18 h compared to placebo and both cicletanine 50 mg and 100 mg. Urinary potassium excretion was also significantly increased in the first 6 h after bendrofluazide compared to placebo, and urine volume significantly increased from 6 to 24 h after bendrofluazide 5 mg compared to placebo and cicletanine 100 mg. Plasma potassium was significantly reduced and plasma renin activity significantly increased 24 h after bendrofluazide 5 mg but these measurements were not significantly different from placebo after cicletanine 50 or 100 mg. These results suggest that cicletanine 100 mg has milder acute natriuretic effects than the thiazide bendrofluazide 5 mg. In contrast cicletanine 50 mg is associated with no major acute renal effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A comparison of the acute effects of cicletanine and bendrofluazide on urinary electrolytes and plasma potassium in essential hypertension. 225 57

Cicletanine is a new antihypertensive agent known for being able to stimulate prostaglandin synthesis in vivo and in endothelial cell cultures. The drug was administered to spontaneously hypertensive rats (SHP-SP) whose hypertension was enhanced by a high sodium content diet. Cicletanine prolonged the animals' survival and reduced the severity of histological renal lesions. PGE2, PGI2 and thromboxane A2 assays performed in renal tissues showed a highly significant increase of PGE2 (a prostaglandin involved in the regulation of renin synthesis) in SHR-SP rats treated with oral cicletanine in daily doses of 30 mg/kg. A less significant increase of PGI2 was found in renal tissues, whereas only slight variations in thromboxane concentrations were observed. The favourable therapeutic effect obtained with cicletanine in the treatment of hypertension may be due, at least in part, to the stimulation of PGE2 and PGI2 production in renal tissue.
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PMID:[Effects of treatment with cicletanine on kidney PGE2 and PGI1 in spontaneously hypertensive rats]. 251 66

The effects of cicletanine, a new antihypertensive agent, on the prostaglandin-kallikrein system and the renin-angiotensin system were studied. A single oral dose of 200 mg cicletanine or placebo was administered to 9 healthy male volunteers, with samples of blood and urine obtained before and 2 hours after drug administration. Cicletanine increased the urine flow, urinary excretion of sodium, and fractional excretion of sodium by 47%, 115%, and 104%, respectively. While the excretion of 6-keto-prostaglandin-F1 alpha was enhanced significantly, urinary excretion of thromboxane-B2, prostaglandin-E2, and kallikrein were unchanged. Cicletanine also did not alter plasma renin activity, plasma aldosterone concentration, or creatinine clearance. These observations suggest that cicletanine may suppress sodium reabsorption at the nephron, and it may stimulate prostacyclin generation with no effect on that of thromboxane-A2. Thus cicletanine may be beneficial in the management of cardiovascular disorders in which the equilibrium between prostacyclin and thromboxane is disturbed.
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PMID:Effects of cicletanine on the urinary excretion of prostanoids and kallikrein, and on renal function in man. 835 79

Cicletanine is a new antihypertensive drug that stimulates renal and vascular synthesis of prostaglandin (PG) I2 in experimental animals. However, there is little evidence that cicletanine increases the level of PGI2 in systemic blood of human subjects. To investigate the short-term antihypertensive mechanism of cicletanine, we measured serially the systemic blood pressure, the levels of 6-keto-PGF1 alpha (a stable metabolite of PGI2) and PGE2, and renin activity in plasma after administration of the drug. Nine patients with essential hypertension on a diet without severe sodium restriction took 100 mg of the drug by mouth. Systemic blood pressure was measured hourly for 24 h before and after cicletanine administration. The two PGs of interest were extracted, purified by high pressure liquid chromatography, and measured by radioimmunoassay. Cicletanine decreased blood pressure 3 and 6 h after administration and increased the plasma level of 6-keto-PGF1 alpha. The increase in 6-keto-PGF1 alpha was small but significant (mean +/- SD, from 3.21 +/- 1.26 to 3.88 +/- 1.44 and later 4.15 +/- 1.08 pg/mL by 3 and 6 h after administration; P < .05 and .01, respectively). The level of PGE2 had increased at 3 h after administration but returned to baseline by 6 h. Plasma renin activity was increased only at 24 h after administration. Cicletanine increased systemic PGI2 levels short-term, producing an antihypertensive effect in patients with essential hypertension.
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PMID:Short-term increase in prostaglandin I2 synthesis caused by cicletanine in patients with essential hypertension. 854 Oct 11