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)

To investigate the possible effects of newly synthesized beta-adrenergic blockers on plasma renin activity, an assay was developed using unanesthetized mice and radioimmunoassay. Renin activity was significantly increased by the administration of hydralazine (1 mg/kg, i.p.), furosemide (20 mg/kg, i.v.), and isoproterenol (0.1 mg/kg, s.c.). Unlike isoproterenol, norepinephrine (1 mg/kg, s.c.) and epinephrine (1 mg/kg, s.c.) were active but considerably less effective stimulants. The increase caused by isoproterenol was blocked by clonidine, pindolol, bunolol, atenolol, and l-propranolol, but not d-propranolol. The beta-blockers with intrinsic sympathomimetic activity such as pindolol were found to increase renin activity when given alone, but blocked an increase in renin activity when given prior to isoproterenol. In general, nonselective beta-blocking drugs possessing both beta 1- and beta 2-(vascular) blocking activity were found to be most effective in blocking plasma renin activity on oral administration.
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PMID:Drug effects on plasma renin activity in the mouse. 617 84

Isoprenaline bitartrate (0.5 microgram/kg/min i.v.) increased the rate of noradrenaline release into the circulation of pentobarbitone-anesthetized rabbits. This increase was much greater than that produced by an equi-hypotensive dose of the vasodilator hydralazine (0.2 mg/kg i.v.), suggesting that it was only partly due to baro-reflex activation of sympathetic nerves. This facilitatory effect of isoprenaline was also observed in the nephrectomized, pithed rabbit, with electrically stimulated sympathetic outflow, ruling out central nervous system and renin-angiotensin effects. ICI 118,551 HCl (0.3 mg/kg + 0.1 mg/kg/h i.v.) blocked the isoprenaline-induced hypotension, but did not affect the isoprenaline-induced tachycardia, suggesting that it selectively blocked beta 2-adrenoceptors. ICI 118,551 totally abolished the isoprenaline-induced increase in noradrenaline release, suggesting a beta 2-effect. Atenolol (0.3 mg/kg + 0.1 mg/kg/h) blocked the isoprenaline-induced tachycardia, a beta 1-effect, but only slightly attenuated the isoprenaline-induced increase in noradrenaline release. Atenolol by itself decreased heart rate and arterial pressure, but there was no reflex rise in the noradrenaline release rate, which suggests that atenolol impairs baroreceptor activation of sympathetic nerves. In another series of experiments, also in the pentobarbitone-anesthetized rabbit, adrenaline was released into the circulation by splanchnic nerve stimulation. This resulted in prolonged increases of adrenaline levels in heart tissue. After the plasma adrenaline levels had returned to prestimulation values, the rate of noradrenaline release into the plasma was enhanced. This increase was not observed in rabbits treated with either desipramine HCl (1 mg/kg i.v.) or propranolol HCl (2 mg/kg i.p.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Local modulation of noradrenaline release in vivo: presynaptic beta 2-adrenoceptors and endogenous adrenaline. 620 19

Immunocytochemical techniques were used for the localization of the different components of the renin-angiotensin system (RAS) within the kidneys of various species. Special attention was paid to the renin-secreting granulated cells located mainly in the media of the afferent glomerular arteriole. It was demonstrated that variations of kidney renin caused by stimulation or inhibition of the RAS are reflected in changes of the length of the renin-positive part of the afferent arteriole upstream from its entry into the glomerulus. During stimulation, plain smooth-muscle cells are transformed into renin-generating granulated cells. Likewise, the marked species differences in kidney renin are paralleled by corresponding differences in the renin-positive part of the afferent vessel. In this context, the site of action and the relative importance of the stimuli inducing renin secretion, i.e., the beta 1-adrenoreceptor, the mechanoreceptor, and the so-called macula densa mechanism are discussed. Whereas the microtopography of the RAS in the kidney has been at least partly understood, little is known about the stimulus-secretion coupling at the level of the individual granulated cell. Thus, adequate electrophysiological data about granulated cells might help to understand some still obscure phenomena, e.g., the inhibitory effect of Ca2+ on renin secretion. Our investigations in the hydronephrotic kidney preparation of the mouse show that granulated cells do not differ significantly from "plain" smooth-muscle cells in their electrical characteristics. They have a membrane potential of -55 mV and are spontaneously active. Both cell types are depolarized by noradrenaline and angiotensin II (AII), although they remain unaffected by isoproterenol. Since isoproterenol is known to stimulate renin secretion, our results indicate that stimulus-secretion coupling via the beta 1-adrenoreceptor is likely to proceed without changes of membrane potential in granulated cells.
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PMID:The afferent glomerular arteriole: immunocytochemical and electrophysiological investigations. 620 47

Sympathetic outflow influences the renal release of renin through modifications of the tonic activity of the renal nerves and the plasma concentration of catecholamines. These influences may initiate changes in the rate of renin secretion or modulate the response initiated by another of the mechanisms that control renin release. Beta-adrenoceptor mediated stimulation of renin release has been demonstrated in vivo, in the isolated perfused kidney and in preparation in vitro. Likewise an array of evidence has accumulated pointing to the existence of alpha-adrenoceptor mediated inhibition of renin release. However, the cellular location, the physiological significance, and even the existence of these alpha-adrenoceptors is still disputed. Receptors sensitive to alterations in the vascular volume have been identified in areas of low and high pressure of the circulation. There is evidence that input from both types of receptors may cancel each other, and that to demonstrate experimentally the effects on renin release of the low pressure cardiopulmonary receptors it is necessary to avoid changes in the input from the high pressure arterial receptors, and vice versa. Again there are dissenting voices that disclaim a tonic inhibitory effect of cardiopulmonary receptor initiated impulses on renin release. The majority of the pharmacological evidence identifies the beta-adrenoceptors in JG cells as of the beta 1-subtype. However, some species may make exception to this generalization. As in other tissues, beta-adrenoceptor mediated influences appear to relate to activation of adenylcyclase in the cell membrane. Considerable interest in the role of calcium in the process of activation of renin release has met with some unexpected, though consistent, experimental findings.
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PMID:Sympathetic control of renin release. 628 85

The respective contributions of beta-adrenoceptor subtypes to the hemodynamic, humoral and metabolic consequences of adrenergic stimulation during graded exercise in man were investigated using nonselective beta-adrenoceptor blockade with propranolol and beta 1-adrenoceptor blockade with atenolol. Doses of these agents that produced comparable suppression of beta 1 response as measured by antagonism of cardioacceleration during exercise were selected. Six healthy, nonsmoking males received these drugs in a placebo-controlled, Latin-square, randomized manner using a double-blind protocol. Both drugs produced comparable reductions of systolic blood pressure and elevation of diastolic blood pressure compared with placebo as exercise load increased. Propranolol produced higher peak epinephrine levels than atenolol or placebo (808 +/- 162, 640 +/- 190 and 584 +/- 153 pg/ml, respectively, p = 0.03), but norepinephrine levels did not show significant differences. Plasma renin activity was similarly suppressed both at rest and during all grades of exercise by both drugs. Lactate levels during moderate exercise were significantly lower after propranolol than after either atenolol or placebo (p = 0.03), but were similar at heavy work loads. Plasma glucose values rose on placebo (from 96.5 +/- 2.1 to 97.7 +/- 2.7 mg/dl) and on atenolol (from 99.7 +/- 2.2 to 102.1 +/- 4.8 mg/dl), but fell on propranolol (from 96.4 +/- 1.9 mg/dl to 87.2 +/- 2.5 mg/dl, p less than 0.01). These results indicate that blockade of vascular smooth muscle beta 2 receptors does not substantially alter hemodynamics during intense short-term exercise. Stimulation of renin release and lipolysis are produced through beta 1-adrenoceptor mechanisms, whereas beta 2 adrenoceptors are important in the provision of carbohydrate as an energy substrate for exercising muscle.
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PMID:Differentiation of hemodynamic, humoral and metabolic responses to beta 1- and beta 2-adrenergic stimulation in man using atenolol and propranolol. 629 12

Anesthetized dogs with isolated carotid sinus preparation were used to examine the mechanisms involved in the increase in renin secretion rate produced by carotid baroreceptor reflex renal nerve stimulation (RNS) at constant renal perfusion pressure. Lowering carotid sinus pressure by 41 +/- 5 mmHg for 10 min increased mean arterial pressure and heart rate, caused no or minimal renal hemodynamic changes, decreased urinary sodium excretion, and increased renin secretion rate. Metoprolol, a beta 1-adrenoceptor antagonist, given in the renal artery, did not affect the decrease in urinary sodium excretion but attenuated the increase in renin secretion rate, from 1,764 +/- 525 to 412 +/- 126 ng/min (70 +/- 8%). Indomethacin or meclofenamate, prostaglandin synthesis inhibitors, did not affect the decrease in urinary sodium excretion but attenuated the increase in renin secretion rate, from 1,523 +/- 416 to 866 +/- 413 ng/min (51 +/- 18%). Addition of metoprolol to indomethacin-pretreated dogs attenuated the increase in renin secretion rate from 833 +/- 327 to 94 +/- 60 ng/min (86 +/- 10%). These results indicate that reflex RNS at constant renal perfusion pressure results in an increase in renin secretion rate that is largely mediated by renal beta 1-adrenoceptors and is partly dependent on intact renal prostaglandin synthesis. The beta 1-adrenoceptor-mediated increase in renin secretion rate is independent of and not in series with renal prostaglandins.
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PMID:Interaction of renal beta 1-adrenoceptors and prostaglandins in reflex renin release. 630 Dec 85

It is uncommon for the small organic compounds used as drugs to possess unique target specificity. Thus, receptor antagonists as well as compounds that inhibit enzymes interact more widely than with their intended targets, actions that at times defeat the selectivity desired in their design. The antibody combining site, because it is a size larger than most drugs, has the capacity for a large number of interatomic contacts with its ligands, which provides the physical basis for increased selectivity and affinity. Two examples are described in applications where highly selective drugs are not available, the inhibition of the enzyme renin and the blockade of the beta 1-adrenergic receptor. Antibody specificity is achieved in the first instance by purifying the immunogen renin. In the second example, an antibody is generated in the absence of a purified beta receptor, by using a beta-blocking drug to generate an antibody that acts as a receptor model and the immunologic principle of anti-idiotypy to provide a second antibody that recognizes the receptor.
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PMID:Immunologic approaches to the inhibition of renin and the adrenergic system. 630 28

The goal of these experiments was to determine if isoproterenol-stimulated renin secretion in the rat is mediated by activation of beta 1- and/or beta 2-adrenoceptors. The rat renal cortical slice preparation was used. The renin secretory rate was a sigmoid function of the logarithm of the isoproterenol concentration; half-maximal and maximal stimulation occurred at approximately 0.01 and 0.1 microM isoproterenol, respectively. Neither timolol (a nonselective beta-antagonist) nor atenolol (a beta 1-selective antagonist) had a significant effect on basal secretory rate, but both shifted the isoproterenol dose-response curve to the right without changing its slope, suggesting competitive antagonism. Timolol was the more potent, but the response to a maximally effective concentration of isoproterenol could be blocked by timolol (0.9 microM), atenolol (110 microM), or a combination of the two (0.45 microM timolol plus 55 microM atenolol). This latter finding is consistent with action of the two antagonists at one and the same site. If it is assumed that timolol antagonizes both beta 1- and beta 2-adrenoceptors and that atenolol antagonizes only beta 1-adrenoceptors, it follows that isoproterenol-stimulated renin secretion in this preparation is mediated by activation of beta 1-adrenoceptors.
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PMID:Evidence that beta 1-adrenoceptor activation mediates isoproterenol-stimulated renin secretion in the rat. 630 47

Several studies report a substantial rise in plasma catecholamines after caffeine. Epinephrine infusion induces a pressor response after nonselective beta-blockade. We studied the hemodynamic and humoral effects of drinking coffee after placebo and after both nonselective (propranolol) and beta 1-selective (metoprolol) blockade in 12 normotensive subjects. After placebo, coffee induced a rise in systolic and diastolic blood pressure and a fall in heart rate, whereas forearm blood flow did not change. Plasma catecholamines, especially epinephrine (+150%), rose and plasma renin activity, fell after drinking coffee. The effects of coffee on blood pressure, forearm blood flow, and all humoral parameters were not altered by pretreatment with propranolol or metoprolol. The fall in heart rate after coffee, however, seemed to be greater during propranolol. We conclude that the rise in plasma epinephrine after coffee was too small to reveal differences in reaction in propranolol- and metoprolol-pretreated subjects.
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PMID:Hemodynamic and humoral effects of coffee after beta 1-selective and nonselective beta-blockade. 634 98

The effects of a single oral dose and of an 8 week treatment with labetalol--an alpha 1- and beta 1-2-adrenoceptor blocking agent--and with atenolol--a beta 1-adrenoceptor blocking agent--were compared in 52 hypertensives. A single oral dose of atenolol induced a marked bradycardia without decrease in blood pressure. On the contrary labetalol lowered blood pressure but not resting heart rate. After an 8 week treatment both drugs exhibited a similar antihypertensive effect. However labetalol did not decrease heart rate and plasma renin activity as markedly as atenolol did. It was concluded that the alpha 1 blocking properties of labetalol were of importance in the development of the antihypertensive properties that this drug exhibits after a single or multiple administrations.
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PMID:[Comparative effects of an alpha 1 and beta 1-2 blocker (labetalol) and a beta-1 blocker (atenolol) in the hypertensive patient]. 635 64


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