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)

DA2 dopamine receptors are present in renal blood vessels and glomeruli. Stimulation of DA1 dopamine receptors leads to renal vasodilation, diuresis, and natriuresis, but a functional role for renal DA2 receptors is largely unknown. We investigated the possible role of DA2 receptors in the control of renal function by intrarenal infusion of a highly specific DA2 agonist, LY 171555 (LY), in conscious uninephrectomized dogs (n = 5) in metabolic balance at sodium intake of 40 meq/day. The infusion of LY at 0.5 pmol.kg-1.min-1 did not change the urinary sodium excretion or renal hemodynamic function. A significant dose-dependent antidiuresis (F = 8.1, P less than 0.0001) and antinatriuresis (F = 93.3, P less than 0.0001) and a decrease in filtration fraction (F = 2.3, P less than 0.02) occurred as the LY dose was increased from 1.0 to 10.0 pmol.kg-1.min-1. There were no changes in systemic plasma renin activity, plasma aldosterone concentration, or mean arterial pressure during intrarenal LY administration. These data suggest that intrarenal DA2 receptor stimulation with LY decreases renal sodium excretion in part by hemodynamic mechanisms. Renal dopamine may act at vascular and/or glomerular DA2 receptors to modulate renal function.
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PMID:Intrarenal DA2 dopamine receptor stimulation in the conscious dog. 135 30

The present study was designed to characterize the developmental changes in the renal responses to dopamine DA1-receptor activation in chronically instrumented preterm (109-115 days) and near-term (130-140 days, full term 145 days) fetal sheep. Cumulative doses of the selective DA1-agonist fenoldopam increased mean arterial blood pressure (MABP) in both preterm (+16 +/- 3%) and near-term fetuses (+16 +/- 3%) but had no significant effect on renal blood flow velocity. Infusion of the DA1-antagonist SCH-23390 did not affect the increase in MABP, suggesting that the effect of fenoldopam on MABP was not directly related to activation of DA1-receptors. Fenoldopam infusion had no significant effects on renal function parameters in preterm fetuses. In near-term fetuses, however, fenoldopam increased urinary flow rate (82.6 +/- 20.9%, P < 0.003), glomerular filtration rate (GFR; 16.6 +/- 4.9%, P < 0.01), urinary sodium excretion (40.1 +/- 14.9%, P < 0.02), and fractional excretion of sodium (26.8 +/- 11.2%, P < 0.03). Infusion of the DA1-antagonist SCH-23390 blocked the fenoldopam-induced diuresis and natriuresis but had no significant effect on the rise in GFR. Fenoldopam infusion had no significant effects on plasma renin activity and plasma aldosterone concentration and on urinary prostaglandin (PG) excretion (PGE2, PGF2 alpha, and 6-keto-PGF1 alpha). Taken together, these results suggest that the renal effect of DA1-receptor activation is age dependent and that stimulation of DA1-receptor in near-term fetuses is associated with a diuresis and natriuresis that seem to be independent of renal hemodynamics and adrenal effects.
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PMID:Ontogeny of renal response to specific dopamine DA1-receptor stimulation in sheep. 135 89

We studied the effects of fenoldopam, a selective dopamine DA1 agonist on systemic and splanchnic hemodynamics, renal blood flow and sodium excretion in 12 patients with alcoholic cirrhosis and ascites. Hepatic, azygos and renal veins were catheterized before and after intravenous administration of fenoldopam, 0.05 micrograms/kg/min for 1 hr and increased to 0.1 micrograms/kg/min for another hour. Mean arterial pressure progressively decreased (from 83 +/- 7 to a minimum of 77 +/- 8 mm Hg 100 min after starting the infusion) but returned to baseline level at 120 min. Plasma norepinephrine and renin activity increased (respectively from 567 +/- 297 to 919 +/- 375 pg/ml, p less than 0.05, and from 17 +/- 14 to 23 +/- 15 ng/ml/hr, p less than 0.05). Renal blood flow, urine output or sodium excretion did not change. Sodium output decreased at 1 hr from 6.9 mumol/min to 4.0 mumol/min, p less than 0.05. Both hepatic venous pressure gradient and azygos blood flow significantly increased by 21%. We conclude that the acute administration of fenoldopam did not improve renal hemodynamics or function in patients with cirrhosis and ascites. In addition, dopamine DA1 agonism caused further increases in norepinephrine concentration and plasma renin activity. Portal pressure also increased, probably because of an increase in mesenteric blood flow. These results question the renal benefit and raise concern about the use of dopamine agonists in patients with cirrhosis and ascites.
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PMID:Selective dopamine DA1 stimulation with fenoldopam in cirrhotic patients with ascites: a systemic, splanchnic and renal hemodynamic study. 167 Oct 29

This review discusses the localization of adrenergic- and dopaminergic-adrenoceptors within the cardiovascular system and describes the cardiovascular and renal changes produced following the activation of these receptors by appropriate agonists. Whereas the role of alpha- and beta-adrenergic agents in the treatment of heart failure is well recognized, recent studies with dopamine (DA)-receptor agonists indicate that they offer a novel approach in the therapy of congestive heart failure. DA-adrenoceptor agonists reduce afterload by causing vasodilation and promote sodium excretion via direct activation of DA1-adrenoceptors located on renal tubules. Fenoldopam is a selective DA1-adrenoceptor agonist found to be effective in heart failure. It reduces afterload by causing peripheral vasodilation and produces natriuresis and diuresis. Dopexamine is a DA1- and beta 2-adrenoceptor agonist, and its efficacy in heart failure is due to its ability to provide mild inotropic support and cause a reduction in afterload. Ibopamine is a prodrug that is converted into its active metabolite, epinine. This compound activates primarily DA1- and DA2-adrenoceptors. It is effective in heart failure, and the mechanism progresses via DA1- and DA2-adrenoceptor-mediated reduction in afterload. Agonists of DA2-adrenoceptors reduce afterload by decreasing the release of norepinephrine and by reducing the levels of renin-angiotensin-aldosterone system. Since both of these systems are active in heart failure, ibopamine offers a rational approach for therapy. The present review addresses the concept of pharmacologic intervention in adrenergic and dopaminergic influence in the cardiovascular and renal systems to produce changes that are desirable for the pharmacotherapy of congestive heart failure.
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PMID:Cardiovascular pharmacology of adrenergic and dopaminergic receptors: therapeutic significance in congestive heart failure. 167 49

Experiments were performed in anaesthetized dogs to characterize the renal effects of the selective dopamine DA1-receptor agonist, fenoldopam. Intrarenal artery infusion of fenoldopam (0.01-10 micrograms/kg per min) caused dose-related renal vasodilation. At low doses (0.01-0.3 micrograms/kg per min), renal vasodilation occurred without concomitant falls in blood pressure but was accompanied by increased urine output. This diuresis was most probably a result of reduced tubular reabsorption since glomerular filtration rate was not increased. Both fenoldopam-induced renal vasodilation and diuresis were blocked to a similar extent by the selective dopamine DA1-receptor antagonist, SCH 23390 (30 micrograms/kg, intravenously), suggesting that both effects were mediated by dopamine DA1-receptors. In the presence of the angiotensin converting enzyme inhibitor, captopril (1 mg/kg, intravenously, + 20 micrograms/kg per min, intrarenal artery), fenoldopam (0.01-0.3 micrograms/kg per min) significantly increased fractional excretion of sodium, despite reducing blood pressure; neither of these effects were observed in captopril-free dogs. These observations support the view that the inhibitory effect of fenoldopam on tubular function, and its vasodepressor activity, may be opposed by angiotensin II resulting from fenoldopam-induced renin release.
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PMID:Effects of dopamine DA1-receptor blockade and angiotensin converting enzyme inhibition on the renal actions of fenoldopam in the anaesthetized dog. 168 41

This review summarizes the results obtained with ibopamine on anaesthesized dogs. Ibopamine is a dopamine-related drug active by oral route, namely the diisobutyric ester of N-methyl-dopamine. Ibopamine is able to activate dopamine specific and adrenergic receptors in the heart and circulation, inducing a vasodilating activity together with a mild positive inotropic effect without increasing heart rate and myocardial O2 consumption. The activation of dopamine and adrenergic receptors mediates a direct vasodilation postjunctional DA1 and beta 2 receptors and an indirect vasodilation (presynaptic DA2 and alpha 2-receptors) through the inhibition of the release in norepinephrine, the renin-angiotensin system, and the secretion of aldosterone and vasopressin, thus antagonizing the neurohormonal alterations in congestive heart failure through a receptor mechanism. Ibopamine can also activate beta 1- and beta 2 and very modestly vascular synaptic alpha 1- and alpha 2-receptors, thus inducing a mild positive inotropic activity and avoiding a drop in arterial pressure which might take place in presence of the intense vasodilation induced by the drug. There is some difference in potency between dopamine and epinine. Epinine is the active metabolite of ibopamine and is more active than dopamine on DA1, DA2, alpha 1, alpha 2 and beta 1 and beta 2 receptors. Ibopamine can be safely associated with captopril and digoxin but not with nifedipine.
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PMID:Pharmacological profile of ibopamine. A summary of experiments on anaesthesized dogs. 198 Jun 31

Dopamine, administered as in intravenous infusion, has shown unique pharmacological properties in the cardiovascular and renal system with respect to the other catecholamines. These properties, which are the basis of its clinical use, have been related to the stimulation not only of beta- and alpha-adrenergic receptors, but of specific dopamine receptors, particularly when dopamine is administered at a low rate of infusion (0.5 to 2 micrograms/kg.min). Peripheral dopamine receptors of the DA1 and DA2 subtype are located in the arterial bed, in prejunctional sympathetic fibres, and probably on specific dopaminergic neurons, and mediate vasodilation either directly or through the control of sympathetic tone. DA1 and DA2 receptors are also located in the kidney and are involved in the control of electrolyte excretion and in renin release; in the adrenal cortex, DA2 receptors exert control on aldosterone release. These findings, and the local synthesis of dopamine in the proximal tubular cells, strongly suggest a physiological role of dopamine in cardiovascular-renal homeostasis in health and disease. Various efforts of expanding and improving the therapeutic use of dopamine have allowed important progress in the understanding of dopaminergic mechanisms in laboratory and clinical pharmacology; the selective DA1 agonist fenoldopam and gludopa, a prodrug delivering dopamine to the kidney, have been particularly useful in this respect. Ibopamine, a prodrug which is able to produce dopamine-like effects on oral administration, has proved its clinical usefulness in the chronic treatment of congestive heart failure, as a monotherapy in mildly affected patient, or in combination therapy in severe patients. In the light of these, and other, results the importance of further effort in pathophysiological and therapeutic research in this field has to be emphasized.
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PMID:Dopamine and the kidney in heart failure. 206 52

In the sympathetic nervous system the physiologic effects of the endogenous catecholamines noradrenaline (NA) and adrenaline (A) are mediated by alpha- and beta-adrenoreceptors (ARs). Both AR-types can be subdivided into two major subtypes: alpha-ARs into alpha-1 (predominant effect: vasoconstriction) and alpha-2 (presynaptic: inhibition of NA-release; postsynaptic: vasoconstriction), beta-ARs into beta-1 (cardiac effects, renal renin release, and lipolysis) and beta-2 (presynaptic: facilitation of NA-release; postsynaptic: vascular, bronchial, and uterine smooth muscle relaxation, glycogenolysis and possibly part of the A-mediated cardiac effects). During the last 30 years growing evidence has accumulated that dopamine (DA), the third endogenous catecholamine and the immediate precursor of NA, may also cause peripheral effects through stimulation of specific DA-receptors, in addition to its known action at alpha- and beta-ARs. It is now well accepted that at least two different DA-receptors are present in many peripheral tissues (DA1 and DA2), including those of the cardiovascular and autonomic nervous system. They seem to be involved in dilation of certain vascular beds, inhibition of NA-release during nerve stimulation, natriuresis, and aldosterone release. In chronic heart failure cardiac beta-AR function decreases (presumably due to endogenous "down-regulation" by the elevated catecholamines), and this decrease is related to the severity of heart failure (judged clinically by New York Heart Association functional class). The human heart contains both functional beta-1 and beta-2 ARs; cardiac beta-1 and beta-2 ARs seem to be differentially affected by different kinds of heart failure; in end-stage dilated cardiomyopathy beta-1 ARs are selectively reduced, whereas beta-2 ARs are nearly normal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Physiology and pharmacology of cardiovascular catecholamine receptors: implications for treatment of chronic heart failure. 224 13

Over the last three years we have carried out studies on the urine output of both sodium and dopamine in five different ethnic groups: whites, Ghanaians, Zimbabweans, Iranians and Thais. Sodium was measured by ion specific electrode and dopamine by HPLC with electrochemical detection (using epinine as an internal standard). In several groups salt loading studies were also carried out. The five ethnic groups differed substantially with regard to the correlation between their urinary sodium and dopamine outputs. Three groups (whites, Thais and Zimbabweans) showed a strong positive correlation (P less than .001) and this may reflect their traditionally salt rich diet. In two groups (Ghanaians and Iranians) there was no correlation and this may reflect a salt scarce environment. Taken together with our previously reported studies showing that normotensive Ghanaians do not mobilize dopamine on salt loading, this would suggest that certain ethnic groups are predisposed to develop hypertension on salt loading--that is, they are 'salt sensitive.' This genetic trait may have passed from the West Coast of Africa, with the slaves, to America and the Caribbean. Other workers have reported deficiencies in vasodilator systems in the American black, such as dopamine, kallikrein and the renal prostaglandins. These defects may lead to the nosologic entity of 'low renin' hypertension, well described in American blacks, and could open up avenues of therapy based either on DA1 activators (such as fenoldopam) or on renal prodrugs (such as gludopa).
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PMID:Ethnic differences in the renal sodium dopamine relationship. A possible explanation for regional variations in the prevalence of hypertension? 238 74

In anesthetized dogs, a 15-min intravenous (i.v.) infusion of fenoldopam (2.0 micrograms/kg/min) produced a decrease in mean aortic blood pressure (MAP) and an increase in renal blood flow (RBF) and plasma renin activity (PRA). The hypotensive effect attained a maximum within 5 min and then waned by approximately 30% at the end of fenoldopam administration. The development of this "tolerance" phenomenon was prevented by enalapril or saralasin. The hypotension and the increase in PRA were not modified by either propranolol or chlorisondamine but were inhibited by SCH 23390, a DA1 antagonist. Fenoldopam (0.1 microgram/kg/min for 15 min) infused into the left renal artery (i.a.) in intact or ganglion-blocked dogs did not change MAP but increased PRA. This effect was antagonized by SCH 23390. In ganglion-blocked preparations in which an apparently maximal renal vasodilatation had been achieved by an i.a. acetylcholine, i.a. fenoldopam produced an increase in PRA which was again blocked by SCH 23390. In uninephrectomized dogs, blockade of alpha- and beta-adrenoceptors or inhibition of renal baroreceptor and macula densa mechanisms of renin release failed to prevent the fenoldopam-induced increase in PRA. In conclusion, the release of renin by fenoldopam is responsible for the development of tolerance to the hypotensive effects of fenoldopam. Furthermore, because the increase in PRA was blocked by SCH 23390 and occurred in the absence of either operational systemic or intrarenal regulatory mechanisms, we propose that it is mediated by stimulation of specific dopamine (DA1) receptors on the juxtaglomerular (JG) cells.
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PMID:Increase in plasma renin activity evoked by fenoldopam in dogs is directly mediated by dopamine1 receptor stimulation. 247 22


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