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)

24 h urinary sodium excretion was used to monitor salt intake in 36 patients with essential hypertension to determine whether limitation of the antihypertensive action of thiazide diuretics could be explained by increased salt appetitie stimulated by salt depletion. Sodium excretion in these patients was similar before treatment to that observed in normotensive controls, and no change was observed during 2 years' treatment with bendrofluazide. However, plasma-renin rose progressively over the 2 years even in 5 of 8 patients whose renin was not stimulated initially by diuretics. Thus, there is no evidence that a voluntary increase in salt intake limits the efficacy of diuretic treatment; on the other hand, progressive stimulation of the renin-angiotensin system may be an important limiting factor to the antihypertensive action of diuretics. If so, the antihypertensive effect of dietary salt restriction may be similarly limited.
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PMID:Salt intake and diuretic treatment of hypertension. 8 56

Captopril, an orally active angiotensin-converting enzyme (ACE) inhibitor, was effective in the long-term reduction of blood-pressure in 17 patients with essential hypertension. The addition of hydrochlorothiazide produced a further hypotensive effect, and the combined treatment produced satisfactory control of the blood-pressure for eight months. Captopril prevented and reversed the secondary hyperaldosteronism and hypokalaemia induced by simultaneous diuretic administration, thus eliminating the need for potassium supplements. The fall in plasma-angiotensin-II and urinary aldosterone and rise in angiotensin I and plasma-renin provide biochemical evidence that captopril inhibits ACE in vivo. No change in circulating venous bradykinin levels could be detected. The hypotensive action of captopril is not mediated by changes in blood-bradykinin but may involve inhibition of the renin-angiotensin and kallikrein-kinin systems locally within the kidneys or blood vessels.
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PMID:Long-term effects of captopril (SQ14 225) on blood-pressure and hormone levels in essential hypertension. 9 Feb 16

Renal hemodynamic effects of chronic prazosin therapy were studied in 10 men and with essential hypertension. Successful antihypertensive therapy was accompanied by diminution in total renovascular resistance, probably at the level of the afferent arteriole. The resistance change was unexplained by alterations in intravascular volume, the vasodilatory renal kallikrein-kinin system, or sympathetic nervous system activity, but was associated with a diminution in plasma renin activity. Potential mechanisms for the resistance decrement are discussed, including renal perfusion autoregulation, diminished activity of the vasoconstrictive renin-angiotensin system, and direct intrarenal afferent arteriolar alpha adrenergic blockade.
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PMID:Prazosin and renal hemodynamics: arteriolar vasodilation during therapy of essential hypertension in man. 9 96

The value of prazosin and methyldopa administration was compared in 16 patients with essential hypertension during a 6 month randomized, double-blind, parallel trial. Both drugs were administered in combination with hydrochlorothiazide, 50 mg twice daily, until recumbent diastolic blood pressure was decreased to less than 90 mm Hg or the patient was receiving prazosin, 5 mg q.i.d., or methylodpa, 500 mg q.i.d. Addition of either prazosin or methyldopa to hydrochlorothiazide lowered blood pressure significantly and to a similar degree without altering plasma renin activity. Heart rate and weight were significantly increased during prazosin, but not methyldopa, therapy. Symptomatic side effects occurred with equal frequency during treatment with both agents and did not result in alteration or discontinuation of therapy in any patient. A decrease in frequency of administration from q.i.d. to b.i.d. or t.i.d./b.i.d. to q.d. did not adversely affect blood pressure control. Substitution of propranolol for prazosin or methyldopa provided similar antihypertensive effectiveness with a significant decrease in heart rate.
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PMID:Comparison of prazosin and methyldopa in essential hypertension: results of a randomized, double-blind, parallel trial. 9 37

Patients with low-renin essential hypertension have certain features consistent with excessive mineralocorticoid activity. Because known mineralocorticoids are normal in the majority of low-renin essential hypertension patients, an unknown mineralocorticoid was sought in the urine of such patients. Urine extracts from patients with low-renin essential hypertension were assayed for mineralocorticoid activity in adrenalectomized rats and found to contain more such activity than could be accounted for by the known mineralocorticoids in the extracts. The factor responsible for the unexplained mineralocorticoid activity was purfied and then identified by mass spectral analysis as 16beta-hydroxydehydroepiandrosterone (16beta-OH-DHEA). Synthetic 16beta-OH-DHEA was found to have a mineralocorticoid potency one-fortieth that of aldosterone in the rat bioassay. The mineralocorticoid effects of both the urine extracts and the synthetic steroid were blocked in the rat by spironolactone, a mineralocorticoid antagonist. A specific assay for 16beta-OH-DHEA was developed, and its level in the urine was found to be elevated in patients with low-renin essential hypertension.
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PMID:Evidence for a new mineralocorticoid in patients with low-renin essential hypertension. 12 32

16beta-Hydroxydehydroepiandrosterone (16beta-OH-DHEA) and related C19-steroids have recently been reported to be etiologic in low-renin essential hypertension. The mineralocorticoid potency of 16beta-OH-DHEA and several C19-steroids (16-oxo-A-diol, 16-oxo-testosterone, 16beta-OH-epiandrosterone, 5-androstene-3beta, 16beta,17beta-triol, 19beta-OH-testosterone, 18-OH-DHEA, and 16alpha-OH-DHEA) were investigated in two different rat bioassay systems under a variety of experimental conditions. In all but one instance, only negligible mineralocorticoid activity was observed, usually less than 0.1 per cent that of aldosterone. Since 16beta-OH-DHEA has negligible mineralocorticoid activity in the rat bioassay and the toad bladder assay (as reported by others), does not cause hypertension when injected chronically into the rat, and does not displace aldosterone from its renal receptors, it appears unlikely to be etiologic in low-renin essential hypertension. On the other hand, when 16-oxo-testosterone was injected intraperitoneally instead of subcutaneously, it demonstrated a slight increase in mineralocorticoid activity (from less than 0.1 per cent to 0.2 per cent) which equaled that of 18-hydroxydeoxycorticosterone (18-OH-DOC) injected subcutaneously. Thus, the possibility remains that 16-oxo-testosterone or a closely related metabolite may have sufficient mineralocorticoid activity to be involved in certain forms of hypertension in man.
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PMID:Mineralocorticoid activity of 16beta-hydroxydehydroepiandrosterone and related steroids. 13 37

The urinary excretion of 3beta,16beta-dihydroxy-5-androsten-17-one (16beta-OH-DHEA) is increased in patients with low renin essential hypertension. This steroid and its isomer 3beta,17beta-dihydroxy-5-androsten-16-one (16-oxo-A) have also been reported to have mineralocorticoid activity in adrenalectomized rats. These findings have led to the postulate that excessive secretion of 16beta-OH-DHEA may be responsible for the production of low renin essential hypertension. In this study unilaterally nephrectomized salt loaded rats injected once a week with 30 mg of 11-desoxycorticosterone acetate per/kg of body weight for 2 month periods developed hypertension. Rats given similar amounts of 16beta-OH-DHEA or 16-oxo-A and rats given no steroids did not develop hypertension. We conclude that it is unlikely that 16beta-OH-DHEA and 16-oxo-A are direct causative factors in the production of low renin essential hypertension.
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PMID:Blood pressure changes following chronic administration to rats of 3beta,16beta-dihydroxy-5-androsten-17-one, 3beta,17beta-dihydroxy-5-androsten-16-one and 21-hydroxy-4-pregnene-3,20-dione-21-acetate. 13 80

The excretion rates and precursors of the 3-sulfate and glucuronide conjugates of 16 beta-hydroxydehydroepiandrosterone (16 beta-OH DHEA) were measured in normotensive controls and in patients with normal and low renin essential hypertension. The hypertensive subjects, and to the greatest degree those of the low renin subgroup, excreted increased amounts of 16 beta-OH DHEA sulfate and glucuronide and lesser amounts of DHEA sulfate and glucuronide than the controls. The major precursor of the urinary 16 beta-OH DHEA sulfate in the hypertensives was circulating DHEA sulfate, whereas the major precursors of 16 beta-OH DHEA glucuronide were DHEA, DHEA sulfate and 17-OH pregnenolone, as determined from their specific activities. Furthermore, both subgroups of hypertensives had similarly elevated DHEA and DHEA sulfate secretory rates compared to the controls. The stimulus to this increased peripheral conversion of circulating 17-OH pregnenolone, DHEA and DHEA sulfate into 16 beta-OH DHEA conjugates in essential hypertension, especially of the low renin type, is unknown.
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PMID:Origin of urinary 16 beta-hydroxydehydroepiandrosterone in essential hypertension. 13 14

An inhibitor of adrenal steroid biosynthesis, aminoglutethimide, was administered to seven patients with low renin essential hypertension, and the antihypertensive action of the drug was compared with its effects on adrenal steroid production. In all patients aldosterone concentrations in plasma and urine were within normal limits before the study. Mean arterial pressure was reduced from a pretreatment value of 117+/-2 (mean+/-SE) mm Hg to 108+/-3 mm Hg after 4 days of aminoglutethimide therapy and further to 99+/-3 mm Hg when drug administration was stopped (usually 21 days). Body weight was also reduced from 81.6+/-7.2 kg in the control period to 80.6+/-7.0 kg after 4 days of drug treatment and to 80.1+/-6.7 kg at the termination of therapy. Plasma renin activity was not significantly increased after 4 days of treatment but had risen to the normal range by the termination of aminoglutethimide therapy. Mean plasma concentrations of deoxycorticosterone and cortisol were unchanged during aminoglutethimide treatment whereas those of 18-hydroxydeoxycorticosterone, progesterone, 17alpha-hydroxyprogesterone, and 11-deoxycortisol were increased as compared to pretreatment values. In contrast, aminoglutethimide treatment reduced mean plasma aldosterone concentrations to about 30% of control values. Excretion rates of 16beta-hydroxydehydroepiandrosterone, 16-oxo-androstenediol, 17-hydroxycorticosteroids and 17-ketosteroids, and the secretion rate of 16beta-hydroxydehydroepiandrosterone were not significantly altered by aminoglutethimide treatment whereas the excretion rate of aldosterone was reduced from 3.62+/-0.5 (mean+/-SE) in the control period to 0.9+/-0.2 mug/24 h after 4 days and to 1.1+/-0.3 mug/24 h at the termination of aminoglutethimide treatment. The gradual lowering of blood pressure and body weight during aminoglutethimide therapy is consistent with the view that the antihypertensive effect of the drug is mediated through a reduction in the patients' extracellular fluid volume, probably secondary to the persistent decrease in aldosterone production. The observation that chronic administration of aminoglutethimide lowered blood pressure in these patients and elevated their plasma renin activity to the normal range without decreasing production of the adrenal steroids, deoxycorticosterone, 18-hydroxydeoxycorticosterone, and 16beta-hydroxydehydroepiandrosterone, makes it unlikely that these steroids are responsible either for the decreased renin or the elevated blood pressure in patients with low renin essential hypertension.
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PMID:Effect of aminoglutethimide on blood pressure and steroid secretion in patients with low renin essential hypertension. 14 41

Plasma renin activity is quantitated by measuring the rate of angiotensin generation during incubation of plasma renin with endogenous renin substrate. The angiotensin is quantitated by radioimmunoassay. Our studies indicate that the incubation step is best carried out in undiluted plasma at the pH optimum for renin (pH 5.7) in the presence of EDTA, neomycin, and DFP or PMSF. By using these conditions, incubation of low-renin samples can be prolonged for up to 18 hr, because angiotensinases and converting enzyme are completely inhibited. Accuracy is enhanced by prolongation of the incubation time, which results in more angiotensin and eliminates the need for blank subtraction. Incubation at pH 7.4 is disadvantageous because of lower rates of generation of angiotensin 1, because of the inability to maintain pH constant without addition of strong buffer, and because the incubation step cannot be prolonged beyond 3 hr. Dilution of plasma is undesirable because it results in a slower reaction rate due to dilution of both enzyme and substrate, and it is not possible to correct for the effect of substrate dilution. The radioimmunoassay of angiotensin I presents few unusual problems. The volume of plasma assayed should be 20 muI or less. If blank subtraction is used, antibodies should be screened to determine the extent to which they bind nonspecific substances in plasma, and then to ascertain whether the blank is entirely additive when angiotensin is added to it. Assay sensitivity is an important issue, since approximately 30 percent of patients with essential hypertension have subnormal plasma renin activity. In a study of three different commercial kits we found that many low-renin samples were undetectable and major fractions could not be discriminated with precision or consistency from normal renin samples. However, the incubation conditions can be easily modified, so that an 18-hr incubation can be utilized and then low-renin samples can be detected with the same degree of accuracy as those with normal plasma renin activity.
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PMID:Radioimmunoassay of plasma renin activity. 16 97


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