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 effects of ouabain or ouabain and furosemide on renal function and renin secretion were studied in conscious isovolemic sheep. The sheep received a continuous renal arterial infusion of papaverine, 7 mg/min, throughout the experiment. Ouabain alone (7 X 10(-7) M in the renal plasma) produced significant decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF) but not in renal perfusion pressure. Plasma [K+] rose after ouabain administration. Fractional (FENa) and absolute (UNaV) Na+ excretion were 2.9 +/- 1.0% (mean +/- SE) and 78 +/- 54 muEq/min, respectively, during the papaverine infusion and rose to 19 +/- 5.1% (P less than 0.05) and 528 +/- 116 muEq/min (P less than 0.01) after ouabain administration. Despite the large changes in Na+ reabsorption, renin secretion was not stimulated. During the control period, renin secretion was 281 +/- 131 ng/min and the average renin secretion after ouabain administration was 310 +/- 78 ng/min (not significant). A smaller dose of ouabain (2 X 10(-7) M) infused into the renal artery with 40 mg of furosemide, iv, did not decrease GFR but RPF was suppressed. FENa and UNaV averaged 4.4 +/- 1.6% and 121 +/- 44 muEq/min, respectively, while papaverine was infused into the renal artery and increased to 18 +/- 4.8% (P less than 0.05) and 636 +/- 209 muEq/min (P less than 0.05) after ouabain and furosemide were infused. Renin secretion was 118 +/- 62 ng/min during the control period and averaged 240 +/- 67 ng/min after ouabain plus furosemide. The difference was not statistically significant. Thus ouabain alone does not stimulate renin secretion in the conscious, isovolemic sheep despite a presumed increase in [NaCl] at the macula densa and inhibition of NaCl transport by the loop of Henle. Ouabain also blocks the normal stimulatory effects of furosemide on renin secretion.
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PMID:Renal function and renin secretion after administration of ouabain and ouabain plus furosemide in conscious sheep. 65 58

1. The effects of different energy substrates, of low temperature, of urea, and of ouabain and ethacrynic acid were studied on the rate of renin release from viable juxtaglomerular cells during superfusion of isolated rat glomeruli. 2. Neither lactate nor glutamate altered renin release rate from that observed using glucose as the sole energy substrate. Succinate 10 mM elevated release transiently but did not influence the release caused by reductions in osmolality through lowering sucrose concentration. 3. Peak renin release was more prolonged and returned more slowly to control following reductions in osmolality in phosphate-Ringer than in bicarbonate-Ringer. 4. At 37 degrees C, the peak of renin released induced by hypo-osmolality was smaller and delayed, and returned earlier to control than at 30 degrees C. Reduction in temperature from 30 to 4 degrees C resulted in a 32-fold increase in basal release rate. At 4 degrees C a 20 m-osmole/kg reduction in tonicity caused an additional 2-5-fold increase in release rate. 6. Increasing superfusate osmolality with urea did not affect basal renin release but 100 mM urea suppressed the releasing effect of a 15 mM reduction in NaCl concentration. 7. Ouabain (10(-4) M) caused a small (33 +/- 9%, P less than 0-025) transient increase in renin release. Ethacrynic acid (10(-3) M) provoked a progressive increase in release reaching 100 +/- 15% above control within 50 min. In the presence of both inhibitors the release provoked by hyposmolality was prolonged. 8. It is concluded that renin release in vitro is a function of actively regulated cell volume and it is proposed that a similar mechanism could underline both barorecptor and macula densa controls of renin secretion in vivo.
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PMID:Studies on renin release from isolated superfused glomeruli: effects of temperature, urea, ouabain and ethacrynic acid. 94 62

The present study investigated the role of ouabain-dependent inhibition of the Na(+)-K+ pump and stimulation of the brain renin-angiotensin system by looking at 1) the short-term and long-term effects of ouabain on arterial blood pressure, and 2) the acute and chronic effects of angiotensin II (ANG II) intraventricularly (i.c.v.) on the release of an endogenous inhibitor of the Na(+)-K+ pump. Ouabain infused subcutaneously in a dose of 1.5 mg.kg-1. 24 h-1 for 7 days did not affect arterial blood pressure in rats, whereas increases in both blood pressure and weight were observed in rats infused with ouabain at the same dose for a 4-week period. Plasma supernate obtained from pentobarbital-anesthetized dogs acutely treated with ANG II (1 microgram i.c.v. every 30 min for 2 h) induced a 44% decrease in the ouabain-sensitive 86Rb uptake by the rat tail artery which was prevented by pretreatment with saralasin i.c.v. Plasma supernate obtained from dogs that were infused for 4 days with ANG II (20 ng/min i.c.v.) and received saline as the drinking fluid also reduced by 34% the ouabain-sensitive 86Rb uptake by the rat tail artery. The present study provides evidence that chronic inhibition of the Na(+)-K+ pump for 4 weeks leads to the development of hypertension and that the release of an endogenous inhibitor of the Na(+)-K+ pump is implicated in the hypertension resulting from chronic stimulation of the brain angiotensin-system and an increase in sodium chloride intake.
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PMID:The ouabain-dependent Na(+)-K+ pump and the brain renin-angiotensin system. 131 74

1. The present experiments were designed to determine the effect of melittin on renin secretion. Melittin is a polypeptide component of bee venom which stimulates phospholipase A2 activity, thereby increasing arachidonic acid release and prostaglandin (PG) synthesis, and which inhibits protein kinase C activity. Either of these actions might be expected to stimulate renin secretion, since renin secretion is stimulated by arachidonic acid and by several PGs, and since renin secretion is inhibited by several activators of protein kinase C. 2. In rat renin cortical slices incubated at 37 degrees C in a buffered and oxygenated physiological saline solution, 0.1-10 microM-melittin produced a concentration-dependent stimulation of both prostaglandin E2 (PGE2) synthesis and renin secretion. However, melittin-stimulated renin secretion is independent of melittin-stimulated phospholipase A2 activity, arachidonic acid release, and PG synthesis, since 20 microM-quinacrine (a phospholipase A2 antagonist) and 50 microM-meclofenamate (a cyclooxygenase antagonist) antagonized basal and melittin-stimulated PGE2 synthesis but had no effects on basal or melittin-stimulated renin secretion. 3. Furthermore, melittin-stimulated renin secretion is not produced by inhibition of protein kinase C, since an activator of protein kinase C (12-O-tetradecanoylphorbol 13-acetate, TPA), enhanced rather than antagonized melittin-stimulated renin secretion. Ouabain partially antagonized, but did not completely block, melittin-stimulated renin secretion. 4. Thus, melittin-stimulated phospholipase A2 activity probably accounts for stimulated PGE2 production, but not for stimulated renin secretion. The mechanism of melittin-stimulated renin secretion is unclear; an effect on protein kinase C does not appear to be involved, and in contrast to the stimulatory effects of a variety of other substances, melittin-stimulated renin secretion is only partially antagonized by ouabain.
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PMID:Effect of melittin on renin and prostaglandin E2 release from rat renal cortical slices. 223 11

Plasma from black male patients with essential hypertension was bioassayed for vascular Na+-K+ pump inhibitory activity. Halves of the same rat tail artery were incubated for two hours in boiled plasma supernates from a hypertensive patient and a paired age-, sex-, and race-matched normotensive subject and then ouabain-sensitive 86Rb uptake was measured. Ouabain-sensitive 86Rb uptake by their leukocytes was also measured. Eighteen pairs of subjects were studied. The uptakes were not significantly different in the hypertensive patients and control subjects. However, when we selected from the eighteen hypertensive patients, nine with low plasma renin activity on the day of the study, uptakes were reduced in the hypertensive patients relative to the paired control subjects. We also assayed plasma supernates from normotensive black and white male subjects before and after acute volume expansion (2.5 L saline IV + 1.5 L distilled water orally over a three-hour period) and from paired normotensive subjects before and after sham volume expansion and obtained a positive bioassay in the expanded subjects both on intraindividual and interindividual comparisons. These studies demonstrate increased vascular Na+-K+ pump inhibitory activity in the plasma of black male patients with low renin essential hypertension and in the plasma of normotensive subjects after acute volume expansion. The findings suggest that the inhibitory activity in the hypertensive subjects' plasma is related to volume expansion, relative or absolute.
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PMID:Humoral Na+-K+ pump inhibitory activity in essential hypertension and in normotensive subjects after acute volume expansion. 266 73

Bartter's syndrome is characterized by chronic hypokalaemia, activation of the renin-angiotensin system and normal blood pressure. To investigate whether a generalized disturbance of sodium-potassium pump function might be of pathogenetic importance, lymphocytic sodium-potassium homeostasis was examined in 5 patients suffering from Bartter's syndrome. Two of the patients were treated with potassium chloride supplementation, the others were without medical treatment when studied. All were severely hypokalemic (serum potassium 2.8 +/- 0.24 mmol/l, mean +/- SEM). Lymphocyte sodium and potassium concentration (14.4 +/- 0.37 and 94.4 +/- 7.7 mmol/l, respectively), ouabain sensitive 22Na-efflux rate constant (2.68 +/- 0.25 h), and absolute ouabain sensitive efflux rate (38.16 +/- 4.2 mmol l-1 h) did not differ from matched controls. Ouabain binding capacity was 126 900 +/- 23 500 sites/cell in patients vs 50 400 +/- 17 900 in controls (p less than 0.05). In conclusion, patients with Bartter's syndrome may have an intrinsic abnormal pump function, characterized by an increased pump density and a low cation turn-over rate per pump unit.
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PMID:Lymphocytic sodium and potassium pump function in Bartter's syndrome. 274 41

Previous studies by others have demonstrated that exogenous adenosine inhibits renin secretion in vivo. In the present experiments, we studied the effects of three adenosine receptor agonists [N6-cyclohexyladenosine (CHA), 2-chloroadenosine (2-CIA) and 5'-N-ethylcarboxamideadenosine (NECA)] on renin secretion of rat renal cortical slices. The effects were biphasic; submicromolar concentrations inhibited secretion concentration-dependently and the order of potency was CHA greater than 2-CIA greater than NECA. Micromolar and higher concentrations stimulated secretion concentration-dependently and the order of potency was reversed: NECA greater than 2-CIA greater than CHA. These results are consistent with the hypothesis that activation of A1 and A2 adenosine receptors produces inhibition and stimulation of secretion, respectively. Theophylline antagonized both the inhibitory effect of low concentrations of CHA and the stimulatory effect of higher concentrations, providing additional evidence for mediation by activation of cell-surface adenosine receptors. Calcium chelation abolished the inhibitory effect of CHA, suggesting that increased intracellular calcium mediates the inhibitory effect; on the other hand, the inhibitory effect was unaffected by membrane depolarization and calcium channel blockade, suggesting that CHA-induced inhibition is not due to calcium influx through voltage-sensitive calcium channels. Ouabain, vanadate and K-depolarization, all of which are believed to increase intracellular calcium, antagonized CHA- and NECA-stimulated renin secretion, suggesting that the stimulatory effect of these agonists is mediated by decreased intracellular calcium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A1 and A2 adenosine receptor activation inhibits and stimulates renin secretion of rat renal cortical slices. 298 63

A circulating Na+, K+-ATPase inhibitor may cause arterial hypertension in patients with suppressed plasma renin activity, either directly or by sensitizing peripheral vessels to alpha-adrenergic stimulation. This hypothesis was tested by evaluating forearm arteriolar (plethysmographic technique) response to exogenous alpha-adrenergic stimulation by a 2-minute intra-arterial infusion of norepinephrine (0.1 microgram/dl tissue per minute) and to Na+, K+-ATPase inhibition by sequential 20-minute intra-arterial infusions of ouabain (0.36 and 0.72 microgram/dl tissue per minute). Two groups of hypertensive subjects with suppressed plasma renin activity, either essential or secondary to aldosterone excess, were compared with age-matched and sex-matched hypertensive subjects with normal plasma renin activity (n = 7 per group). No significant differences in forearm vascular response to norepinephrine were found among the three groups. Ouabain caused a highly significant, dose-related increment in forearm vascular resistance that was not accompanied by changes in the contralateral limb or systemic blood pressure. No significant interindividual differences in vascular responsiveness to ouabain were found. The individual increments in forearm vascular resistance during ouabain administration were unrelated to basal values or to plasma aldosterone, norepinephrine, or potassium concentrations. These data are not consistent with the hypothesis that suppressed basal Na+, K+-ATPase activity is primarily a characteristic of hypertensive patients with unresponsive plasma renin activity. Overall, these results cast doubts on the possibility of linking the development of human low renin hypertension to an endogenous Na+, K+-ATPase inhibitor.
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PMID:Vascular responses to ouabain and norepinephrine in low and normal renin hypertension. 301 54

1. Studies of erythrocyte cation transport mechanisms in vitro were performed on eight normotensive, premenopausal female subjects at the mid-points of the follicular and luteal phases of their menstrual cycles. Concurrent plasma concentrations of 17 beta-oestradiol, progesterone, aldosterone and renin activity were measured. 2. Ouabain-resistant, frusemide-resistant rubidium influx (an index of passive potassium diffusion) was significantly lower in the luteal than the follicular phase. 3. In further studies in four of the eight subjects, the mean rate constant of the rubidium influx measurement was also lower in the luteal than in the follicular phase. 4. There were no changes in Na+-K+ co-transport, sodium pump activity or intracellular cation concentrations throughout the cycle. 5. There was a tenfold fall in the mean plasma 17 beta-oestradiol/progesterone ratio, as well as increases in plasma aldosterone concentration and renin activity between the mid-follicular and mid-luteal phases. 6. We conclude that changes in plasma oestrogen/progesterone ratio during the menstrual cycle may be associated with alterations in passive potassium diffusion.
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PMID:Erythrocyte cation fluxes during the menstrual cycle in normal female subjects. 330 85

Effects of ouabain on the autoregulation of renal blood flow (RBF) and renin release were examined in filtering and nonfiltering kidneys of anesthetized dogs. Autoregulation of RBF was observed in both kidneys; however, autoregulation in the nonfiltering kidney was comparatively less efficient. These findings indicate that both the myogenic mechanism via a sensor element in the afferent arteriole, a so-called baroreceptor, and the tubuloglomerular feedback mechanism via the macula densa are essential for complete autoregulation. In both the control and nonfiltering kidney, intrarenal arterial infusion of ouabain abolished the autoregulation of RBF and glomerular filtration rate, with no change in the renal vascular sensitivity to vasoactive substances or in renin release induced by pressure reduction. Since various vasoactive drugs elicited a normal vascular response, it appears that the site of action of ouabain was not the vascular contractile elements; at least, an impairment of autoregulation during ouabain infusion was apparently not due to a defect in these elements. These results suggest the possible existence of another mediator, a sensor element in the afferent arteriole that is affected by ouabain. Ouabain may abolish the autoregulation of RBF and renin release via a modification of this baroreceptor in the afferent arteriole as well as through inhibition of the macula densa.
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PMID:Effects of ouabain on autoregulation of renal blood flow in dogs. 351 May 63


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