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)

Investigations in animals indicate that urapidil has a number of actions that may be relevant to its antihypertensive effect. It has an alpha 1-blocking action, a weak beta 1-blocking effect, an interaction with a serotonin receptor and a central depression of sympathetic tone. Urapidil is well absorbed orally with a bioavailability of about 70% and a time to peak concentration of about 4 hours after a sustained release capsule. It is metabolized in the liver at a half-life of 4.7 hours. Peripheral alpha 1-blocking activity has been demonstrated in humans. A shift to the right in the dose-response curve to phenylephrine has been found after urapidil, whereas responses to angiotensin are not affected. Evidence for beta 1-blocking activity is marginal. Urapidil does not inhibit the exercise increase in heart rate. Some investigators have suggested a possible inhibition of isoprenaline tachycardia; others have found no evidence. There is some evidence suggestive of a central action of urapidil in humans as lower single doses result in a decrease in blood pressure and an increase in heart rate. With higher doses the hypotensive effect continues but the tachycardia no longer occurs. However, urapidil has been reported to increase noradrenaline levels, although there has been a report with a high dose reducing vanillylmandelic acid excretion. Evidence for changes in renin is inconsistent. Hemodynamic studies have revealed findings that are compatible with peripheral alpha 1 blockade. After intravenous administration, peripheral resistance is reduced along with arterial pressure, and cardiac output is increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Urapidil, a multiple-action alpha-blocking drug. 256 63

Animal investigations suggest that the mechanism of the antihypertensive effect of urapidil may be complex. Suggestions have included an alpha 1-blocking action, a weak beta 1-blocking effect, an interaction with a serotonin receptor and a central depression of sympathetic tone. Peripheral alpha 1-blocking activity has been demonstrated in man, and a shift to the right in the dose-response curve to phenylephrine has been found after administration of urapidil, while responses to angiotensin are not affected. Evidence for beta 1-blocking activity is marginal, but urapidil does not inhibit the exercise-induced increase in the heart rate, and there is only some suggestion of a possible inhibition of isoprenaline-induced tachycardia. Possible central activity may be deduced from the observation that while lower single doses reduce blood pressure and increase the heart rate, with higher doses the hypotensive effect continues but the tachycardia no longer occurs. However, lower doses of urapidil lead to an increase in noradrenaline levels, while changes in renin are less constant, but there has been a report that a high dose reduced vanillylmandelic acid excretion. Urapidil reduces peripheral resistance along with arterial pressure, and cardiac output is increased. In spite of a reduced arterial pressure, renal blood flow is maintained, presumably due to dilation of renal vessels. Urapidil is well absorbed orally with a bioavailability of about 70% and a tmax at about 4 h after a sustained release capsule. It is metabolized in the liver with a t1/2 of 4.7 h. In conclusion there is evidence that urapidil is an alpha 1-blocking drug in man.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical pharmacology of urapidil. 290 95

Ketanserin, a serotonin receptor antagonist (S2), lowered blood pressure in patients with essential hypertension; at three months 72% (13/18) had a successful reduction in pressure. No marked orthostatic changes were noted. Older patients responded better when standing. Compared with metoprolol, ketanserin provided no significant difference in response at three months. With ketanserin, the heart rate was reduced only in the supine position, whereas it was reduced in the supine and standing positions with metoprolol. Response to ketanserin could not be predicted from baseline renin, aldosterone, or cortisol levels in blood, nor were there any changes in these factors or in plasma hydroxyindole levels with therapy. Ketanserin was generally well tolerated. Cholesterol values were significantly reduced with ketanserin, and there were no adverse hematologic or biochemical changes. Ketanserin should have a significant role in managing hypertension.
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PMID:Comparison of ketanserin and metoprolol in the treatment of essential hypertension. 354 16

To determine if serotonin plays a role in the regulation of renin secretion, pentobarbital-anesthetized dogs were injected intravenously with drugs which modify serotonin metabolism. Renal perfusion pressure was kept constant by a clamp on the aorta proximal to the renal arteries. 5-Hydroxytryptophan (5-HTP) caused a significant increase (p less than 0.05) in arterial plasma renin activity (pra) that was abolished when peripheral and central aromatic amino acid decarboxylase activities were inhibited by administration of benserazide, but not reduced when only the peripheral decarboxylase activities were inhibited by administration of carbidopa. The serotonin receptor blocking drug metergoline also abolished the renin response to 5-HTP. L-Tryptophan in two different doses increased PRA. This increase was not reduced by carbidopa but was reduced or abolished by benserazide, metergoline, and renal denervation. The increase in PRA produced by 5-HTP and L-Tryptophan occurred without any change in blood pressure. 5-HTP had no effect on heart rate but L-Tryptophan reduced heart rate. These data indicate that 5-HTP and L-Tryptophan act on the central nervous system to produce an increase in renin secretion that is mediated via the renal nerves and occurs without a concomitant increase in sympathetic output to the heart or blood vessels. The increase appears to be due to the release of serotonin within the central nervous system.
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PMID:Pharmacological evidence that stimulation of central serotonergic pathways increases renin secretion. 698 77

Central cholinergic mechanisms are suggested to participate in osmoreceptor-induced water intake. Therefore, central injections of the cholinergic agonist carbachol usually produce water intake (i.e., thirst) and are ineffective in inducing the intake of hypertonic saline solutions (i.e., the operational definition of sodium appetite). Recent studies have indicated that bilateral injections of the serotonin receptor antagonist methysergide into the lateral parabrachial nucleus (LPBN) markedly increases salt intake in models involving the activation of the renin-angiotensin system or mineralocorticoid hormones. The present studies investigated whether sodium appetite could be induced by central cholinergic activation with carbachol (an experimental condition where only water is typically ingested) after the blockade of LPBN serotonergic mechanisms with methysergide treatment in rats. When administered intracerebroventricularly in combination with injections of vehicle into both LPBN, carbachol (4 nmol) caused water drinking but insignificant intake of hypertonic saline. In contrast, after bilateral LPBN injections of methysergide (4 microg), intracerebroventricular carbachol induced the intake of 0.3 M NaCl. Water intake stimulated by intracerebroventricular carbachol was not changed by LPBN methysergide injections. The results indicate that central cholinergic activation can induce marked intake of hypertonic NaCl if the inhibitory serotonergic mechanisms of the LPBN are attenuated.
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PMID:Serotonergic mechanisms of the lateral parabrachial nucleus and cholinergic-induced sodium appetite. 1183 5

Various childhood mood disorders are being treated with serotonin selective reuptake inhibitors (SSRIs) such as fluoxetine (Prozac(R)), yet limited data are available on their effects on serotonergic systems prior to maturation. This study investigated the effects of chronic fluoxetine treatment on 5-HT2A serotonin receptor-mediated neuroendocrine responses in young male rats. Prepubescent male rats were treated with saline or fluoxetine (10 mg/kg/day, i.p.) for 14 days, a treatment regimen producing maximal changes in postsynaptic 5-HT2A function in adults. Eighteen hours post-treatment, the rats received saline or increasing doses (0.5, 2.0, or 5.0 mg/kg, i.p.) of the 5-HT2 receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl ((+/-)-DOI). Trunk blood was obtained to determine changes in oxytocin, ACTH, corticosterone, and renin responses. Fluoxetine produced a small ( approximately 6%) but significant reduction in body weight gain, but no changes were observed in basal hormone levels. In both saline- and fluoxetine-treated rats, (+/-)-DOI increased plasma oxytocin levels in a dose-dependent manner. However, the magnitude of the oxytocin responses to all doses of (+/-)-DOI were markedly attenuated ( approximately 50%) in the fluoxetine-treated rats, indicating a functional reduction in the E(max) of 5-HT(2A) receptor-mediated oxytocin responses. In contrast, fluoxetine did not alter the (+/-)-DOI-induced increases in plasma ACTH, corticosterone, or renin. These data provide the first demonstration of selective neuroadaptive responses in 55-HT2A serotonin receptor function due to prepubescent treatment with fluoxetine. These data may be clinically relevant with respect to the use of selective serotonin reuptake inhibitors in children and adolescents.
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PMID:Fluoxetine treatment of prepubescent rats produces a selective functional reduction in the 5-HT2A receptor-mediated stimulation of oxytocin. 1608 47

It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors for the disease and are older than 50 years; (2) who have been diagnosed with unilateral age-related macular degeneration in order to prevent damage of the contralateral eye; (3) who have bilateral age-related macular degeneration in order to avert deterioration and in the hope of a potential improvement. However, randomised prospective clinical trials are still needed to elucidate the potential role of these drug treatments in the prevention and treatment of age-related macular degeneration.
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PMID:[Pharmacological therapy of age-related macular degeneration based on etiopathogenesis]. 2654 69