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)

1. The effects of ouabain on renin secretion by rat renal cortical slices were studied. 2. Renin secretion was inhibited by 10(-3) M-ouabain in the presence of free Ca (10(-4) to 2.6 x 10(-3) M). Inhibition was blocked at Ca less than 10(-8) M. 3. The effect of free Ca on ouabain-inhibition was shown to be independent of the presence of EGTA, completely reversible, and unrelated to passive leakage of renin from non-viable cells, as assessed by simultaneous release of lactate dehydrogenase activity (LDH). 4. It is proposed that, as a result of inhibition of Na, K-ATPase by ouabain, (a) intracellular Na increases in the renin-secreting juxtaglomerular cells, (b) intracellular Ca increases, via an Na-Ca exchange mechanism, and (c) that Ca accumulation, in some unknown manner, inhibits renin secretion.
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PMID:Possible mechanism of the inhibitory effect of ouabain on renin secretion from rat renal cortical slices. 11 99

In the serum of two infant sisters with a congenital renal salt-losing syndrome, Na was rather low and K considerably increased. Even with Na levels of 126 mval/1, sodium was excreted in the urine. Creatinine and hippurate clearances were normal. Primary disturbances of the steroid metabolism were not detectable; plasma cortisol was normal, aldosterone and renin were compensatorily increased. Treatment with DOCA was unsuccessful. Whereas the first infant died (in another hospital), the second one throve well with high oral substitution of NaCl. There was no pathological findings other than a moderate hyperplasia of the juxtaglomerular apparatus, in a kidney biopsy. Except for minimal activity in the ascending limb of Henle's loop, there was no membrane bound Na, K-ATPase in the microdissected tubules. This finding most probably explains the renal salt loss, as this enzyme is necessary for the transcellular flow of sodium and potassium.
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PMID:Tubular Na, K-ATPase deficiency, the cause of the congenital renal salt-losing syndrome. 12 30

The effect of calcium antagonist nifedipine (N) was studied in the changes of blood pressure, total peripheral resistance, activity of the transport membrane ATPase of erythrocyte ghosts, the plasma level of digitalis-like factor and the plasma renin activity. The studies were performed in 10 healthy volunteers and in 19 hypertensive patients after the intake of a single dose of 20 mg N. The changes were studied in the hypertensives after the intake of the drug in daily doses of 3 times 10 mg over 4 weeks, too. The systolic and diastolic blood pressure and peripheral resistance of the forearm decreased in hypertensives after a single dose of nifedipine as well as after the treatment with 30 mg daily over 4 weeks (170.8/109.5 vs 145.3/98.3 mmHg). As compared with the membrane ATPase activity of normotensives, that of the hypertensives was distinctly depressed (0.403 vs 0.321 mumol P(i).mg-1.h-1; p less than 0.01), while after N treatment, the enzyme activity increased to values of those of the normotensives 0.403 mumol P(i).mg-1.h-1). The mean peripheral resistance was not significantly depressed after the long-term treatment with N (2,085 vs 1,535 dyn.s-1.cm-5), while in several hypertensives (9 of 19) a distinct reduction was measured. Analogous results were found in case of the mean renin activity and the activity of several hypertensives after the N treatment. The N effect on the membrane ATPase system is discussed in connection with the hypothesis of Blaustein [1977] (Na(+)- with consecutive Ca(2+)-overload of the cell) and a possible influence of the drug on the electrolyte transport via membrane.
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PMID:The reactivity of peripheral vessels of normo- and hypertensives. 131 13

To evaluate the antihypertensive and hormonal effects of oral magnesium supplementation, 17 inpatients with untreated, uncomplicated mild-to-moderate essential hypertension (EH) and 8 age-matched normotensive controls (controls) were given MgO orally 3 times a day at a daily dose of 1.0 g (0.6 g per day as Mg) for a period of 2 weeks. Supplementation of MgO elicited a significant fall in averaged mean blood pressure calculated with a 24-h ambulatory blood pressure monitoring system (MBP) in EH from a baseline value of 104.3 +/- 12.2 to 99.5 +/- 11.6 mmHg (p < 0.05), while controls remained unaltered from a baseline value of 85.1 +/- 11.5 to 84.5 +/- 13.3 mmHg. The percentage reductions in systolic and diastolic blood pressures were similar during daytime and nighttime in EH. According to the extent of reduction in MBP with magnesium supplementation, EH patients were divided into 2 groups, responder and nonresponder. The level of plasma renin activity (PRA) in the responder group was significantly higher than that of the nonresponder group (p < 0.05). After 2 weeks of magnesium supplementation, the plasma level of Na+, K(+)-ATPase inhibitory activity (PATPI), defined as equivalency to ouabain, was reduced significantly from 0.75 +/- 0.54 to 0.40 +/- 0.30 mumol ouabain/ml (p < 0.05) in the responder group, while it remained unaltered in controls and the nonresponder group. PRA, plasma aldosterone concentration, urinary epinephrine and norepinephrine excretion, and urinary sodium excretion did not change significantly in either control subjects or EH (responder and nonresponder groups). A significant negative correlation existed between the pretreatment PRA and changes in MBP after magnesium supplementation in EH (r = -0.65, p < 0.01), and there was a significant positive correlation between changes in PATPI and changes in MBP as a whole (r = 0.41, p < 0.05). These results support the view that oral magnesium supplementation is a useful approach to treatment of patients with uncomplicated essential hypertension, especially those with high plasmas renin activity. It appears that magnesium suppresses circulating Na+,K(+)-ATPase inhibitory activity to attenuate vascular tone, and thereby reduces blood pressure in EH.
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PMID:Effects of dietary magnesium supplementation on diurnal variations of blood pressure and plasma Na+, K(+)-ATPase activity in essential hypertension. 133 97

Cardiac glycosides in man inhibit renin secretion, probably through a direct effect at the renal level (i.e. inhibition of juxtaglomerular cell Na/K ATPase). Since there is evidence that the human adrenal possesses an intrinsic renin-angiotensin system, we investigated the effect of digoxin on the in vitro generation of renin and angiotensin II/III, as well as of aldosterone, by the human adrenal gland. Minced normal adrenal tissues were studied in a superfusion system, measuring in the 15-min superfusate fractions active renin by immunoradiometric assay and angiotensin II/III and aldosterone by radioimmunoassay, respectively. In a first set of four experiments using different concentrations of digoxin in sequence for 45 min periods, digoxin 10(-5), but not 10(-8) and 10(-6) mol/l, significantly reduced renin and angiotensin II/III output from adrenals, while no change in aldosterone was observed. In a second set of three experiments, the addition of digoxin 10(-5) mol/l for 120 min caused a sustained reduction of renin and angiotensin II/III, but not of aldosterone. In the final experiment, the decrease of renin and angiotensin II/III during superfusion with digoxin 10(-5) mol/l was significantly greater than that observed during superfusion with digoxin in the presence of antidigoxin antibodies. Our data indicate that digoxin at high doses reduces renin and angiotensin II/III but not aldosterone secretion by the human adrenal gland. This suggests two different effects of digoxin, probably both mediated by inhibition of the Na/K ATPase activity, on the adrenal renin-angiotensin- and aldosterone-secreting cells.
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PMID:Effect of digoxin on the in vitro secretion of renin and angiotensin II/III immunoreactivity by the human adrenal gland. 141 45

In addition to demonstrating evidences of increased sympathetic nervous system activity and marked left ventricular hypertrophy in salt-sensitive hypertensives, our group has also reported increased weight gain with salt overload in these patients. The increased weight gain suggests volume expansion, a situation already shown to increase plasma levels of a Na, K-ATPase inhibitor. Therefore, in the present study, digoxin-like factor (DLF) serum levels, spontaneous salt ingestion, nifedipine hypotensive effect, and plasma renin activity were evaluated in essential hypertensive subjects. Thirteen essential hypertensive outpatients were studied sequentially on an ad lib diet, a low salt diet (LSD = 30 mEq Na/day), and a high salt diet (HSD = LSD + 171 mmol/L NaCl/day), 1 week each. On the seventh day of LSD and HSD, DLF levels, mean blood pressure (MBP) response to nifedipine (10 mg sublingual), and plasma renin activity were measured. The MBP percent change from the seventh day of LSD to the seventh day of HSD (salt sensitivity) ranged from -13.7 to 20.9%. A positive correlation (r = 0.64, P < .01) was observed between salt sensitivity and 24-h urinary sodium excretion with an ad lib diet. The DLF serum levels correlated with the salt sensitivity both on LSD (r = 0.50, P < .05) and on HSD (r = 0.53, P < .05). Salt sensitivity was positively correlated with the difference of response to nifedipine between HSD and LSD (r = 0.78, P < .001). Plasma renin activity correlated inversely with DLF on LSD (r = -0.51, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Higher salt consumption, digoxin-like factor, and nifedipine response are associated with salt sensitivity in essential hypertension. 141 33

In addition to cyclooxygenase and lipoxygenase, arachidonic acid (AA) is metabolized by the cytochrome P-450 monooxygenase system. The kidney is one of the major extrahepatic tissues that display cytochrome P-450 enzyme activities, in particular the cortex, specifically the proximal tubule demonstrate the highest concentration. AA is metabolized by the renal cytochrome P-450 epoxygenase and omega/omega 1 hydroxylases to epoxyeicosatrienoic acids and omega/omega-1 alcohols (20- and 19-mono-hydroxyeicosatetraenoic acids), respectively. These metabolites possess a broad spectrum of biological and renal effects which include: vasodilation, vasoconstriction, inhibition and stimulation of Na(+)-K(+)-ATPase, inhibition of ion transport mechanisms, natriuresis, inhibition of renin release and stimulation of cell growth. These metabolites are endogenous constituents of the kidney and are present in urine with increasing concentration under pathological conditions such as pregnancy-induced hypertension. The cytochrome P-450-dependent metabolism of AA is specifically localized to the proximal tubule and exhibits developmental changes, i.e., renal production of metabolites is very low in the fetus, newborn and up to 3 weeks of age, after which a remarkable increase in enzyme activities is observed. These characteristics call attention to the importance of this enzyme system in producing cellular mediators for regulating renal function in normal and diseased states.
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PMID:The renal cytochrome P-450 arachidonic acid system. 145 35

Chronic lead exposure may cause hypertension in normotensive rats. This hypertensinogenic effect has been attributed to perturbations in the renin-angiotensin axis, the contractile response of the vascular smooth muscle, or the intracellular Ca2+ homeostasis as a consequence of the inhibition of Na(+)-K(+)-ATPase activity. In this study we examined the short-term effect of lead exposure on blood pressure, plasma renin activity, vascular contractility, and renal Na(+)-K(+)-ATPase activity and abundance in the spontaneously hypertensive rat. Our data indicate that modest lead exposure caused blood pressure elevation within two weeks in this rat strain that is genetically susceptible to the development of hypertension. This rapid blood pressure-elevating effect did not appear to depend on the mechanisms described in hypertension associated with more chronic lead exposure listed above. This acute model provides an additional approach to the study of lead-induced hypertension.
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PMID:Rapid hypertensinogenic effect of lead: studies in the spontaneously hypertensive rat. 154 88

Atrial natriuretic factor is the main natriuretic hormone. It is a peptide secreted by the atria in response to an increase of the central blood volume. Its effects are opposed to those of the renin angiotensin system and all result in the decrease of volemia. The main of them are an increase in renal sodium excretion, decrease in vascular resistance, increase in capillary permeability, and inhibition of renin and aldosterone secretions. ANF stimulates, via its B receptors, the production of cyclic GMP which is its second messenger. ANF is catabolized by clearance receptors which internalize it and ectoenzymes, mainly neutral endoproteinase. Plasma ANF increases in various conditions for three essential reasons: increase of its secretion from the usual sources, increase of its secretion from supplementary sites, decrease of its catabolism. Since ANF is implied in the maintenance of homeostasis in several diseases, treatment by neutral endoproteinase inhibitors which increases plasma ANF has been considered. Another natriuretic factor structurally close to digitalin and inhibiting Na(+)-K+ ATPase has been described but not identified.
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PMID:[Natriuretic factors]. 160 57

To evaluate the importance of an endogenous sodium pump inhibitor in the pathogenesis of low renin human hypertension, the urinary excretion of a digoxin-like immunoreactive substance (DLIS) was measured in eight patients with primary aldosteronism (n = 5, with adenomas) during two sequential 1-week periods of low- (20 mmol/l NaCl) and high- (200 mmol/l NaCl) sodium intake. DLIS excretion increased consistently during high-sodium intake while urinary aldosterone, plasma renin activity, cortisol and adrenocorticotropic hormone did not change. Although blood pressure showed a time-course parallel to that of the urinary DLIS, the blood pressure increments were not accompanied by evidence of vasoconstriction since forearm blood flow (plethysmographic technique) increased and forearm vascular resistances were reduced. Moreover, the reactivity of forearm arterioles to local norepinephrine was unchanged during the period of low- and high-salt intake, despite the fact that an endogenous sodium pump inhibitor should, supposedly, sensitize the responses to an adrenergic agonist. Finally, forearm vasoconstrictor responses to ouabain, a pharmacological Na+,K(+)-ATPase antagonist, were potentiated during the high-salt diet, a result not expected if an increased number of sodium pumps were occupied by an endogenous inhibitor. These results provide unequivocal evidence for a modulation by salt intake of the urinary excretion of a DLIS in patients with primary aldosteronism. This substance might participate in the regulation of body fluid volume in this syndrome and possibly in other physiological conditions. However, no evidence could be found for a cause--effect relationship between blood pressure and DLIS increments during high-salt intake, at least during the short-term course of the study.
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PMID:Does a digoxin-like substance participate in vascular and pressure control during dietary sodium changes in patients with primary aldosteronism? 164 66


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