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 pentobarbital-anesthetized rats, SK&F 87516 (1.25-80 micrograms/kg/min intravenously over 15 min), the fluoro analog of the selective DA-1 dopamine receptor agonist fenoldopam produced dose-related decreases in carotid artery blood pressure that faded during the infusion period. These effects were abolished by SCH 23390, prolonged by ritanserin, but unchanged by bilateral vagotomy, atenolol, ICI 118,551, idazoxan, methylatropine or S-sulpiride. SK&F 87516 also inhibited the hypotensive effects of clonidine and of the DA-1 receptor agonist fenoldopam, but not of acetylcholine. In pithed rats, SK&F 87516 produced a biphasic vasopressor response. The initial phase was enhanced by SCH 23390 and converted to a transient hypotension by idazoxan. The secondary response was inhibited by ritanserin and enalapril. In pithed, but not in intact rats, SK&F 87516 increased plasma renin activity. In intact rats, SK&F 87516 produced dose-related bradycardic effects that were inhibited (50%) by idazoxan, methylatropine or bilateral vagotomy and abolished by chlorisondamine or pithing. In pithed rats pretreated with either saline or idazoxan, SK&F 87516 reduced the tachycardia to electrical stimulation of preganglionic more than that to postganglionic cardioaccelerator nerve fibers. However, it did not modify heart rate increases evoked by intravenous norepinephrine. In conclusion, SK&F 87516 produces hypotension via vascular DA-1 receptor stimulation. The fading of this effect during the infusion of SK&F 87516 may be related to the partial agonist property of this compound at DA-1 receptors and the stimulation of 5-hydroxytryptamine-2 receptors. SK&F 87516 also behaves as a partial agonist at alpha-2 adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:SK&F 87516, a close analog of fenoldopam, is a partial agonist at dopamine-1 and alpha-2 receptors and produces stimulation of 5-hydroxytryptamine-2 receptors in the cardiovascular system of the rat. 167 75

Seventeen normotensive, premenopausal women were treated with the 5-hydroxytryptamine-reuptake inhibitor dexfenfluramine 30 mg per day, for 4 days in a randomised double-blind, cross-over, placebo controlled trial. Energy intake was held constant during the study as the aim was to study the endocrine and metabolic effects of dexfenfluramine dissociated from its weight-lowering properties. Body weight, blood glucose, plasma insulin, cholesterol triglycerides and C-peptide after an overnight fast and during an oral load of 100 g glucose did not change after dexfenfluramine compared to placebo. Supine and standing systolic and diastolic blood pressures were significantly decreased, while heart rate remained unchanged. Plasma noradrenaline and plasma renin were markedly reduced by dexfenfluramine, and cortisol, beta-endorphin and thyroid hormones were not changed. Thus, dexfenfluramine has a significant hypotensive effect in normotensive, obese women after 4 days of treatment, independent of a negative energy balance. This was associated with decreased circulating plasma noradrenaline, indicating decreased sympathetic nerve activity. Dexfenfluramine may be a candidate drug for longer-term trials in the treatment of primary hypertension associated with obesity.
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PMID:Haemodynamic, metabolic and endocrine effects of short-term dexfenfluramine treatment in young, obese women. 206 May 60

It has not yet been demonstrated clearly whether the antihypertensive action of ketanserin is due to 5-hydroxytryptamine type-2 (5-HT2)-serotonergic receptor blockade or to alpha 1-adrenergic receptor blockade. The present study was performed to evaluate in vivo the antihypertensive action of ketanserin in comparison with that of terazosin, a selective alpha 1-adrenoceptor antagonist. The changes of renal blood flow (RBF) after intrarenal injection of phenylephrine, 5-HT, or angiotensin II were measured in anesthetized rabbits. RBF responses induced by these vasoconstrictors with or without pretreatment with ketanserin (0.2, 1.0, and 5.0 mg/kg, i.v.) or terazosin (0.04, 0.2, and 1.0 mg/kg, i.v.) were examined. Following intrarenal injection, RBF decreased by 20.8%, 22.7%, and 23.0% respectively, without ketanserin and also decreased by 21.0%, 21.6%, and 24.4%, respectively, without terazosin. Following pretreatment with a small dose of ketanserin or terazosin, the vasoconstricting effects of phenylephrine were attenuated by 20% or 62% (delta% changes in RBF), respectively. The effects of 5-HT on RBF responsiveness were blocked by ketanserin in a dose-dependent manner. Ketanserin did not modify the RBF responses to angiotensin II. These findings indicate that the antihypertensive effect of ketanserin, to a certain extent, depends on the blockade of the 5-HT2-serotonergic receptor in addition to that of the alpha 1-adrenoceptor, whereas the renin-angiotensin system is not involved in the hypotensive effects of ketanserin.
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PMID:Differences in vasodilating action between ketanserin, a 5-HT2-serotonergic receptor antagonist, and terazosin, an alpha 1-adrenoceptor antagonist, in anesthetized rabbits. 244 76

Plasma and urine levels of an endogenous digitalis-like compound (EDLC) are increased in low renin Na+-dependent experimental hypertension, in some normotensive offspring of hypertensive patients and in some essential hypertensive patients. Urine-drived EDLC was purified from 550 L of urine from essential hypertensive patients (n = 8) and from normotensive subjects with a family history of hypertension (n = 27), using flash chromatography on C18 reversed-phase, anion exchange chromatography and various reversed-phase high performance liquid chromatographies. The mechanism of Na+-K+ ATPase inhibition and the related effects of semipurified urine-derived EDLC were studied and compared with those of ouabain. Its action was similar to that of ouabain in 8 out of 10 of the tests applied. The main effects of such a compound were the depression of Na+-K+ pump activity of human erythrocytes, the inhibition of 5-hydroxytryptamine reuptake by human platelets, and the induction of natriuresis in urethanized rats. Therefore, EDLC may be considered as one of the natriuretic hormones whose mechanism of action closely resembles that of ouabain.
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PMID:An endogenous digitalis-like compound extracted from human urine: biochemical and chemical studies. 282 38

This report summarizes studies aimed to characterize pharmacologically, hemodynamically and biochemically DA-1 (fenoldopam) and DA-2 (quinpirole) dopamine receptor agonists in anesthetized rats. Fenoldopam (20 micrograms/kg/min i.v. over 15 min) and quinpirole (10 micrograms/kg/min i.v. over 15 min) share the common property of decreasing mean carotid artery blood pressure by lowering peripheral vascular resistance. Fenoldopam increased mesenteric and renal blood flows whereas quinpirole decreased the former blood flow, but enhanced the latter. These effects of quinpirole were antagonized selectively by S-sulpiride, but not SCH 23390; however, with fenoldopam the reverse was found. In chlorisondamine-pretreated rats with blood pressure supported by vasopressin, fenoldopam, but not quinpirole, caused hypotension. In nephrectomized rats, the blood pressure effects of fenoldopam (assessed as area under the infusion time-response curve) were more pronounced than in sham-operated controls. The hypotensive effects due to an i.v. bolus injection of fenoldopam, but not to acetylcholine, histamine, salbutamol or quinpirole, were significantly inhibited in rats pretreated with an infusion of fenoldopam. In pithed rats, quinpirole reduced the pressor responses to electrical stimulation of the spinal cord without affecting those to exogenous norepinephrine, angiotensin II or 5-hydroxytryptamine which, on the contrary, were inhibited by fenoldopam. The plasma renin activity (in intact rats) was reduced by quinpirole, but elevated by fenoldopam. The latter effect also occurred in pithed rats and was blocked by SCH 23390. Quinpirole lowered heart rate, whilst fenoldopam produced tachycardia. These effects of quinpirole and fenoldopam were significantly inhibited by S-sulpiride and SCH 23390, respectively. In chlorisondamine-pretreated rats quinpirole failed to change heart rate whereas fenoldopam still increased it. In conclusion, these results indicate that DA-1 and DA-2 dopamine receptor agonists can be easily discriminated on the basis of their cardiovascular profiles.
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PMID:Cardiovascular characterization of DA-1 and DA-2 dopamine receptor agonists in anesthetized rats. 288 15

In normotensive anesthetized rats, 15-min IV infusions of quinpirole (2.5-40.0 micrograms/kg/min) produced dose-related, rapidly appearing, and long-lasting decreases in mean carotid artery BP and HR. Hemodynamically, the hypotensive effects of quinpirole (10.0 micrograms/kg/min) were due to a fall in total peripheral vascular resistance inasmuch as CO did not undergo significant changes. Mesenteric, hindquarter, and renal blood flows were, respectively, reduced, unchanged, and increased by quinpirole; thus, the renal vascular resistance fell more than either the total peripheral or hindquarter vascular resistance. Biochemically, the hypotensive effects of quinpirole were accompanied by a decrease in the plasma level of norepinephrine and plasma renin activity. The peak fall in blood pressure produced by quinpirole was not significantly modified by atenolol, idazoxan, ranitidine, SCH 23390 (DA1 dopamine receptor antagonist), enalapril, or SK&F 100273 (V1 vasopressin receptor antagonist), but was entirely blocked by S-sulpiride or removal of autonomic nerve drive to the cardiovascular system with chlorisondamine. The effect of quinpirole on systemic and regional vascular resistances was antagonized by S-sulpiride. Furthermore, SK&F 100273 prevented the fall in mesenteric flow produced by quinpirole. Intracerebroventricular injection of quinpirole (10.0 micrograms/kg over 2 min) in saline- or SK&F 100273-pretreated rats produced the same hypotensive effects as an identical IV dose of the compound. In pithed rats, quinpirole (10 micrograms/kg/min IV over 15 min) decreased pressor responses to electrical stimulation of spinal cord outflow without affecting those to exogenously injected angiotensin II, B-HT 920, cirazoline, norepinephrine, or 5-hydroxytryptamine. This inhibitory effect was antagonized by S-sulpiride. The bradycardia produced by quinpirole in intact rats was mediated by the autonomic nervous system inasmuch as it was slightly modified by bilateral vagotomy, partly reduced by atenolol, and entirely prevented by pithing even when the low HR of the last preparation had been raised by IV infusion of isoprenaline. Furthermore, S-sulpiride, but not SCH 23390 or idazoxan, antagonized this effect. In pithed rats, quinpirole similarly inhibited the tachycardic responses elicited by electrical stimulation of either the spinal cord outflow (preganglionic) or postganglionic cardioaccelerator nerve fibers. This effect of quinpirole was susceptible to S-sulpiride but not idazoxan blockade. Finally, in conscious spontaneously hypertensive rats (SHR) but not in normotensive rats, quinpirole (10 micrograms/kg/min IA over 15 min) lowered blood pressure.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cardiovascular characterization of the DA2 dopamine receptor agonist quinpirole in rats. 289 67

Ketanserin, an antagonist highly selective for 5-hydroxytryptamine (serotonin) type 2 (S2) receptors, was given as monotherapy in a dose of 40 mg b.i.d. to 24 subjects with mild to moderate essential hypertension. Its effects were evaluated in a placebo-controlled double-blind crossover study. The effect on blood pressure in 18 subjects was monitored by 24-hour ambulatory intra-arterial measurements. Systolic and diastolic intra-arterial pressures were significantly lowered by ketanserin both during the day and at night, whereas heart rate was unchanged. Cuff pressure readings (triplicate measurements) with the London School of Hygiene sphygmomanometer and an automatic device (12 measurements in 1 hour) in the outpatient clinic also showed a significant effect on both supine and standing pressures. No postural hypotension was noted. Ketanserin had no effect on endogenous creatinine clearance, serum cholesterol levels, and the plasma levels of norepinephrine, renin, and aldosterone. The only side effect that was significantly more common with ketanserin than with placebo treatment was an increase in body weight. Ketanserin may have a place in the treatment of mild to moderate essential hypertension.
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PMID:Chronic effect of ketanserin in mild to moderate essential hypertension. 293 97

The present study was designed to investigate the effect of distinct serotonin (5-HT1A and 5-HT2) agonists and antagonists on renin and corticosterone secretion. Low doses of the selective 5-HT1A agonists 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) (5.0-500.0 micrograms/kg, i.p.) and ipsapirone (TVX Q 7821; 0.5-2.5 mg/kg, i.p.), and of the 5-hydroxytryptamine (5-HT) agonist MK-212 (2.0 mg/kg, i.p.), did not elevate plasma renin activity (PRA) and concentration (PRC) 30 min postinjection. Administration of a higher dose of MK-212 (10.0 mg/kg, i.p.) and of higher doses of ipsapirone (5.0-10.0 mg/kg, i.p.), as well as the 5-HT releaser, fenfluramine (5.0 mg/kg, i.p.), resulted in large increases in PRA and PRC. The effects of MK-212 and fenfluramine on PRA and PRC were blocked by pretreatment with the selective 5-HT2 antagonist, LY53857, in a dose-dependent (0.3-1.0 mg/kg, i.p.) manner. LY53857 (1.0 mg/kg, i.p.) by itself did not affect PRA or PRC. LY53857, furthermore, unmasked a renin-suppressive effect of MK-212, since injection of MK-212 (10.0 mg/kg, i.p.) following LY53857 administration led to a reduction in PRA and PRC. MK-212 (2.0 and 10.0 mg/kg), the high doses of 8-OH-DPAT (500.0 micrograms/kg), ipsapirone (1.0-10.0 mg/kg), and fenfluramine (5.0 mg/kg) all produced an increase in plasma corticosterone levels. The effects of MK-212 and fenfluramine on corticosterone were not inhibited by pretreatment with LY53857. These data suggest that 5-HT1A receptors do not play a role in the regulation of renin secretion, whereas stimulation of 5-HT2 receptors enhances renin release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effects of serotonin (5-HT1A and 5-HT2) agonists and antagonists on renin and corticosterone secretion. 295 98

Systemic administration of serotonin (5-hydroxytryptamine, 5-HT) to non-deprived rats increased saline (0.9%) consumption (5-HT hyperdipsia), without altering saline preference in two-bottle test. When sodium saccharin (0.1%) was the test solution 5-HT suppressed both consumption and preference. 5-HT saline hyperdipsia was blocked by pretreatment with an angiotensin I converting enzyme inhibitor (MK421) and mimicked by isoprenaline-induced stimulation of renin production; saccharin consumption and preference were unaffected by either drug. However, methysergide (a 5-HT antagonist) attenuated the effects of 5-HT on saccharin consumption and preference, thus confirming that these effects are mediated via peripheral 5-HT receptors. It is suggested that the effects of 5-HT on saline consumption are mediated via stimulation of the renin-angiotensin system, but its effects on saccharin consumption and preference are mediated by a separate mechanism at some point subsequent to peripheral 5-HT receptors.
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PMID:Pharmacological investigations of the mechanisms underlying the effects of peripheral 5-HT on flavour consumption and preference. 301 91

Pharmacological enhancement of 5-hydroxytryptamine (5-HT) transmission increases plasma vasopressin in rats. To investigate whether this effect is mediated through activation of the peripheral renin-angiotensin system, plasma vasopressin concentrations were measured after 5-HT activation in rats with lesions of the subfornical organ or pretreated with saralasin. The results show that the 5-HT-induced elevation of vasopressin is not due to activation of the peripheral renin-angiotensin system.
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PMID:Vasopressin release after enhanced serotonergic transmission is not due to activation of the peripheral renin-angiotensin system. 353 8


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