Increment In Plasma Renin Activity Research Articles

Renal nerves: time for reassessment of their role in hypertension?

Renal nerves: time for reassessment of their role in hypertension?

Association Between Activated Renin Angiotensin System and Bone Formation in Hemodialysis Patients: Is the Bone Mass Genetically Determined by ACE Gene Polymorphism?

Background. Angiotensin II (ang II) receptor subtype I binding sites has been recently demonstrated on bone cell precursors. Ang II stimulates DNA and collagen synthesis in human adult bone cells. The aim of this study is to evaluate the role of renin angiotensin system in the bone metabolism and to address the genetic influence of angiotensin converting enzyme (ACE) gene polymorphism on bone mass in hemodialysis patients. Methods. Forty‐eight end‐stage renal disease patients (28 male, 20 female mean age 42 ± 13 years,) on maintenance hemodialysis were included in the study. Bone mineral density (BMD) was estimated at lumbar spine and T score worse than − 1.5 were considered as osteopenia. Serum parathyroid hormone (iPTH) and osteocalcin (OC), bone alkaline phosphatase (bAP) and carboxy terminal propeptide type 1 collagen (PICP) levels were measured as markers of bone metabolism. Plasma renin activity (PRA), serum ACE activity and ACE gene polymorphism (II, ID, DD) were determined. Results. Bone mineral density and T score of the hemodialysis patients were 0.92 ± 0.17 g/cm2 and − 1.36 ± 1.50, respectively. Twenty‐one patients (43,7%) were osteopenic (T score worse than − 1.5) and mean T score of osteopenic patients was − 2.72 ± 0.72. T score of nonosteopenic group was − 0.29 ± 0.99. Serum calcium, serum, phosphorus, serum OC, serum bAP, serum PCIP, serum PTH levels were similar in osteopenics and nonosteopenics. No difference was observed in predialysis PRA and in both pre‐ and postdialysis serum ACE activity of patients in both groups. PRA after hemodialysis in nonosteopenic group was higher than osteopenics (p < 0.05). Percent increment in PRA in hemodialysis patients was correlated with T score (R = 0.48 p < 0.05). Serum ACE activity was positively correlated with serum iPTH (R = 0.29, p = 0.02), serum OC (R = 0.35, p = 0.01), serum bAP (R = 0.34, p = 0.01), serum PCIP (R = 0.36, p = 0.01). T score (− 0.7 ± 1.5, vs − 1.7 ± 1.3 p < 0.05) was higher in DD group (n = 19) compared to II + ID group (n = 29). Conclusions. Association of biochemical and radiological signs of increased bone formation with activated RAS in hemodialysis patients might be an evidence for the involvement of this system in the regulation of bone metabolism.

Atrial natriuretic peptide and sodium homeostasis in compensated heart failure.

The purpose of this study was to determine whether high plasma levels of atrial natriuretic peptide (ANP) in compensated heart failure are important in the maintenance of sodium balance. This was achieved by subjecting eight dogs to bilateral atrial appendectomy (APX) to blunt the ANP response to pacing-induced heart failure. Five intact dogs served as controls. In controls, 14 days of left ventricular pacing at 240 beats/min produced a sustained fall in cardiac output and mean arterial pressure of approximately 40 and 20%, respectively; compared with cardiac output, reductions in renal blood flow (up to approximately 25%) were less pronounced and even smaller decrements in GFR occurred (up to 9%). Despite these changes and a threefold elevation in plasma norepinephrine concentration, plasma renin activity (PRA) did not increase and sodium balance was achieved during the second week of pacing in association with a six- to eightfold rise in plasma levels of ANP. Similar responses occurred in four dogs in which APX was relatively ineffective in blunting the ANP response to pacing. In marked contrast, there were substantial increments in PRA and in plasma norepinephrine concentration, and marked sodium and water retention during the last week of pacing in four dogs with APX and severely deficient ANP. These results indicate that ANP plays a critical role in promoting sodium excretion in the early stages of cardiac dysfunction.

Indirect evidence for vascular uptake of circulating renin in hypertensive patients.

To evaluate whether, in the forearm of hypertensive patients with different circulating renin profiles, local beta-adrenergic receptor-induced production of active renin, plasma renin activity, angiotensin I (Ang I), and angiotensin II (Ang II) was or was not related to the renin profile, we studied four groups of patients: 1) hypertensive patients with primary aldosteronism and suppressed circulating plasma renin activity values (0.15 +/- 0.1 ng Ang I/mL per hour; n = 7), 2) essential hypertensive patients with low (0.47 +/- 0.1 ng Ang I/mL per hour; n = 8) circulating plasma renin activity values, 3) essential hypertensive patients with normal (2.48 +/- 0.52 ng Ang I/mL per hour; n = 8) circulating plasma renin activity value, and 4) renovascular hypertensive patients with high circulating plasma renin activity values (4.16 +/- 2.1 ng Ang I/mL per hour; n = 10). Isoproterenol was infused into the brachial artery, and active renin, plasma renin activity, and Ang I and Ang II forearm balance (venous-arterial differences corrected for forearm blood flow by strain-gauge plethysmography) were measured. Despite a comparable vasodilation, beta-adrenergic stimulation failed to release active renin, plasma renin activity, and Ang I and Ang II in primary aldosteronism. It slightly increased them (except for Ang I) in low renin patients but determined a local production in normal renin and renovascular hypertensive patients. The individual increments in plasma renin activity and Ang II release induced by isoproterenol showed a correlation with the renin profile.(ABSTRACT TRUNCATED AT 250 WORDS)

Hormonal and circulatory responses to chronically controlled increments in right atrial pressure

To study the time-dependent changes in the secretion of atrial natriuretic peptide (ANP) in response to chronic stimulation by controlled increments in atrial pressure, we developed methodology for precise control of right atrial pressure (RAP) in dogs by employing an externally adjustable occluder around the pulmonary artery and a servo-control system. During 7 days of servo-control of RAP at 6.3 +/- 0.1 mmHg above control levels (1.3 +/- 0.1 mmHg), the 24-h coefficient of variation in RAP was 1/45 the variation that occurred under control conditions. After 30 min of increased RAP, mean arterial pressure (MAP) was reduced from 101 +/- 4 to 84 +/- 3 mmHg in association with increments in plasma renin activity (PRA) from 0.6 +/- 0.1 to 2.5 +/- 0.9 ng angiotensin I (ANG I).ml-1.h-1 and in the plasma concentrations of ANP, arginine vasopressin (AVP), and epinephrine from 93 +/- 18 to 484 +/- 61 pg/ml, from 0.5 +/- 0.1 to 9.2 +/- 2.4 pg/ml, and from 82 +/- 27 to 585 +/- 133 pg/ml, respectively. In comparison, on day 7 of servo-control of RAP, sodium balance was achieved and MAP remained depressed (82 +/- 4 mmHg) along with sustained increments in both plasma ANP concentration (482 +/- 67 pg/ml) and PRA (1.7 +/- 0.6 ng ANG I.ml-1.h-1); on the other hand, the plasma concentrations of AVP and epinephrine returned to control levels. This quantitative study indicates that ANP secretion does not chronically adapt to stimulation by increased atrial pressure and suggests that the plasma levels of ANP achieved in heart failure markedly increase renal excretory capability and allow fluid balance to be achieved at a substantial fall in renal perfusion pressure.

Furosemide Dynamics: Influence of Dietary Sodium and of Saralasin

The influence of dietary sodium and saralasin on the natriuretic and diuretic response to furosemide (5 mg/kg i.v.) was studied in three groups of conscious rabbits maintained for 4 weeks on either a normal sodium diet (NSD), or a low sodium diet (LSD) or a high sodium diet (HSD). Neither the sodium content in the diet nor saralasin affected glomerular filtration rate or renal plasma flow. Compared to the NSD, an LSD did not affect the furosemide-induced increment in urinary excretion of sodium (dUNaV) but increased the increment in urinary excretion (dUV) (p less than 0.05). An HSD reduced the furosemide-induced dUNaV and dUV (p less than 0.05). Plasma renin activity (PRA) increased following furosemide administration in animals on an NSD and an LSD, but not in those on an HSD. Independent of diet, a positive correlation occurred between the increment in PRA and the dUNaV (p less than 0.001). Saralasin increased PRA and decreased baseline urinary excretion of sodium (UNaV). In addition, in rabbits on an LSD, saralasin reduced the furosemide-induced dUNaV and dUV by 34 and 27% (p less than 0.05), respectively. It is concluded that furosemide-induced diuresis is increased in rabbits on an LSD and decreased in rabbits on an HSD. In animals on an LSD, the increase in furosemide response appears to be associated with changes in the activity of the renin-angiotensin system and in rabbits on an HSD, the decrease in furosemide effect is probably the net result of several factors.

Reduced increments in plasma renin activity and catecholamines during exercise in Type 1 (insulin-dependent) diabetic patients

Reduced increments in plasma renin activity and catecholamines during exercise in Type 1 (insulin-dependent) diabetic patients

Effects of aging on responses to furosemide

Furosemide causes both diuretic and non-diuretic changes in renal function. We compared responses to intravenous furosemide 0.5 mg.kg −1 in 38 subjects (30 males, 8 females) aged 18 to 30 with those in 14 subjects (9 males, 5 females) aged 50 and over. There were no consistent differences attibutable to gender. Older persons showed greater natriuresis (47 percent in males and 26 percent in females) but their increment in plasma renin activity was markedly reduced. The urinary excretion of thromboxane B 2 was elevated in older subjects (58±10 vs. 30±4 ng/4 h, p<0.05 for males; 48±7 vs. 29±4 ng/4 hr, p<0.05 for females) while that of 6-keto prostaglandin F 1alpha was not different. While differences in the diuretic response to furosemide may be due to pharmacokinetic differences, the non-diuretic response differences may reflect age related changes in renal prostaglandin synthesis.

Testing the “redirection hypothesis” of prostaglandin metabolism in the kidney

Furosemide increases the synthesis of two major renal eicosanoids, prostacylin (PGI 2) and thromboxane A 2 (TXA 2), by stimulating the release of arachidonic acid which in turn is metabolized to PGG 2/PGH 2, then to PGI 2 and TXA 2. PGI 2 may mediate, in part, the early increment in plasma renin activity (PRA) after furosemide. We hypothesized that thromboxane synthetase inhibition should direct prostaglandin endoperoxide metabolism toward PGI 2, thereby enhancing the effects of furosemide on renin release. Furosemide (2.0 mg.kg −1 i.v.) was injected into Sprague-Dawley rats pretreated either with vehicle or with U-63, 557A (a thromboxane synthetase inhibitor, 2 mg/kg −1 followed by 2 mg/kg −1.hr −1). Urinary 6ketoPGF 1 α and thromboxane B 2 (TXB 2), reflecting renal synthesis of PGI 2 and TXA 2, as well as PRA and serum TXB 2, were measured. Serum TXB 2 was reduced by 96% after U-63, 557A. U-63, 557A did not affect the basal PRA. Furosemide increased PRA in both vehicle and U63, 557A treated rats. However, the PRA-increment at 10, 20 and 40 min following furosemide administration was greater in U-63, 557A-treated rats than in vehicle-treated rats and urine 6ketoPGF 1 α excretion rates were increased. These effects of thromboxane synthesis inhibition are consistent with a redirection of renal PG synthesis toward PGI 2 and further suggest that such redirection can be physiologically relevant.

Effect of cyclooxygenase and thromboxane synthetase inhibition on furosemide-stimulated plasma renin activity.

We studied the effects of a specific thromboxane (TX) synthetase inhibitor (U-63,557A) and a cyclooxygenase inhibitor on furosemide-induced renin release. Furosemide (2.0 mg X kg-1) was injected into Sprague-Dawley rats pretreated with indomethacin (10 mg X kg-1, i.v.), U-63,557A (1.0-32.0 mg X kg-1, i.v.), or vehicle (Na2CO3 0.03 M). Plasma renin activity was measured in blood samples collected 0, 10, 20, and 40 min after the injection of furosemide. Blood was also collected after the administration of vehicle, indomethacin, or U-63,557A for serum TXB2, a measure of platelet TXA2 synthesis. The results demonstrated that plasma renin activity rose with time following furosemide in the various groups of rats; indomethacin suppressed the furosemide-induced increments in plasma renin activity, while U-63,557A at doses of 4-8 mg X kg-1 augmented it. At doses below 4 mg X kg-1 or above 8 mg X kg-1, U-63,557A did not augment renin secretion. Indomethacin and U-63,557A reduced serum thromboxane by 81 and 90%, respectively. Thus, these experiments suggest that thromboxane synthetase inhibition, within a narrow dosage range, potentiates furosemide-induced renin release while cyclooxygenase inhibition suppresses it.

Role for aldosterone in blood pressure regulation of obese adolescents

To determine the role of aldosterone in the regulation of blood pressure (BP) in obese adolescents, supine and 2-hour upright plasma renin activity (PRA), and aldosterone and cortisol were measured in 10 nonobese and 30 obese adolescents before and after a 20-week weight loss program. The obese adolescents had significantly higher supine and 2-hour upright plasma aldosterone concentrations (17 ± 8 vs 6 ± 2 ng/dl [p < 0.01 supine obese vs nonobese] and 30 ± 11 vs 14 ± 8 ng/dl [p < 0.01 2-hour upright]). Although PRA was not significantly different between the 2 groups of children, a given increment in PRA produced a greater increment in aldosterone in the obese adolescents. In addition, obese subjects had a significantly increased mean BP (93 ± 12 vs 74 ± 8, p < 0.005) and a weak correlation between BP and plasma aldosterone concentration. Compared with an obese control group, weight loss resulted in a significant decrease in plasma aldosterone (p < 0.01) without an associated decrease in PRA. After weight loss there was also a significant decrease in the slope of the posture-induced relation between PRA and aldosterone. In addition to weight loss being associated with a significant decrease in BP (p < 0.01), there was a significant correlation between the change in plasma aldosterone and the change in mean BP (r = 0.538; p < 0.002 change in upright aldosterone vs change in mean BP). Obese adolescents have an increased plasma aldosterone concentration that may be important in the regulation of their BP.

Renin secretion by the spontaneously diabetic rat.

Renal function studies and measurements of in vivo plasma renin activity (PRA), kidney renin content, and renin secretion by isolated, perfused kidneys were performed in spontaneously diabetic and nondiabetic BioBreeding/Worcester (BB/W) rats. Diabetic animals evidenced hyperglycemia, glycosuria, and plasma volume expansion. After dietary sodium deprivation, plasma volume fell to levels equivalent to those of sodium-deprived, nondiabetic rats. Dietary sodium deprivation evoked a larger proportional increase in PRA among diabetic than nondiabetic animals, although PRA before sodium restriction was equivalent in the two groups. Basal renin release (RR) was higher from isolated, perfused kidneys from diabetic rats than from nondiabetic kidneys. Diabetic kidneys, moreover, displayed increased kidney renin content (KRC). By contrast, while isoproterenol (10(-5) M) stimulated a nearly fivefold increment in RR from nondiabetic, perfused kidneys, a negligible effect was observed in diabetic kidneys. The dose-response curve of renin secretion (as a proportion of total renal content) in response to isoproterenol was shifted downward. Hence, while KRC and spontaneous RR by isolated, perfused kidneys were increased, the increment in PRA with salt depletion and the renin-secretory response to isoproterenol in vitro were impaired. We propose that specific defects in renin secretion, in particular, the response to beta-adrenergic stimulation, may be operative in diabetes.

Enhanced responses to pressor stimuli by intracerebroventricular infusions of angiotensin II in conscious rats.

Effects of the intracerebroventricular (IVT) infusion of a subpressor dose (3 ng/kg/min) of angiotensin II (ang II) on the pressor responses to intravenous (IV) infusions of ang II and to IV bolus injections of norepinephrine (NE) were studied in conscious rats. This study was undertaken to determine whether activations of the brain renin-angiotensin system alter pressor responsiveness to IV infusions of ang II and IV injections of NE in the conscious state. Pressor responses to IV infusions of ang II and IV injections of NE were potentiated by the concurrent IVT infusion of the subpressor dose of ang II. Plasma renin activity (PRA), plasma corticosterone (B), and plasma prolactin concentration (PRL) were also measured before and during the IVT infusion of the subpressor (3 ng/kg/min) or the pressor (50 ng/kg/min) dose of ang II in order to determine the mechanisms for this pressor hyperresponsiveness to vasoconstrictor substances. The IVT subpressor dose of ang II increased PRA, but did not significantly change B and PRL. The IVT pressor dose of ang II decreased PRA and increased B, but did not significantly change PRL. These results suggest that the brain renin-angiotensin system plays an important role in pressor responsiveness to IV ang II and NE. Although the mechanisms are not fully understood, pressor hyperresponsiveness to IV ang II and NE by an intracerebroventricularly administered subpressor dose of ang II may be related to increased sympathetic outflow, because of the increment in PRA.

Effect of intravenous epinephrine infusion on plasma renin activity in adrenalectomized dogs

Previous experiments have shown that circulating epinephrine stimulates renin secretion and increases plasma renin activity (PRA) when it is infused intravenously, but not when it is infused directly into the renal artery at similar infusion rates. The present experiments were designed to test the hypothesis that the adrenal glands mediate the PRA response to intravenous epinephrine infusion. Accordingly, anesthetized dogs were prepared with either an acute bilateral adrenalectomy or a sham-adrenalectomy procedure. Epinephrine was then infused intravenously into each animal for 45 minutes at a rate of 25 ng·kg −1·min −1. Time control experiments in which epinephrine was not infused were also conducted. In sham-adrenalectomized dogs, PRA (in nanograms per ml h −1) rose from 4.1 ± 1.4 in the control period to 13.0 ± 3.0 during intravenous epinephrine infusion (means ± SE; p < 0.01). In adrenalectomized dogs, PRA rose from 2.1 ± 0.4 during the control period to 5.5 ± 0.9 during intravenous epinephrine infusion (p < 0.01). Neither the absolute increments in PRA nor the percent increases in PRA were significantly different between the two groups receiving epinephrine. PRA remained unchanged in time control experiments. These data demonstrate that the adrenal glands need not be present in order for intravenous epinephrine infusion to elicit an increase in PRA. The data do not support the hypothesis, therefore, that epinephrine-induced increases in PRA are initiated by receptors located within the adrenal glands.

Beta-Endorphin stimulates plasma renin and aldosterone release in normal human subjects.

To determine the effect of beta-endorphin on the renin-angiotensin-aldosterone system, human synthetic beta-endorphin (0.3, 1.0, and 3.0 micrograms/kg X min) was infused iv in normal subjects. Each dose was administered for 30 min, and a control infusion of 5% dextrose and water was given on another day. Ten subjects were studied recumbent and in balance while ingesting a 10-meq Na+ diet. Plasma renin activity (PRA), plasma aldosterone (PA), and plasma cortisol (F) were measured basally and every 30 min for 210 min. The increments in PRA and PA above basal significantly (P less than 0.05) increased (3.1 +/- 1.2 ng/ml X h and 12.2 +/- 5.3 ng/dl, respectively; P less than 0.05) at the end of the beta-endorphin infusion. beta-Endorphin also significantly (P less than 0.01) suppressed F levels. Since in the low salt study, beta-endorphin suppressed F release while stimulating renin secretion, an additional five subjects were pretreated with dexamethasone (0.5 mg every 6 h) and were studied in balance while ingesting a 200-meq Na+ diet to suppress the renin-angiotensin system. Significant (P less than 0.025) increments in PRA (2.1 +/- 0.7 ng/ml X h) and PA (4.1 +/- 1.7 ng/dl) levels above basal were again found during the sequential dose infusion of beta-endorphin (0.3, 1.0, and 3.0 micrograms/kg X min). However, PA elevations were sustained for at least 120 min after the beta-endorphin infusion was stopped despite a drop in PRA 90 min earlier. In additional studies, an attempt was made to define the minimal effective dose of beta-endorphin by 60-min infusions (0.03, 0.1, and 0.3 micrograms/kg X min) in subjects on a 200-meq Na+ diet who were dexamethasone pretreated. The PRA and PA levels rose significantly (P less than 0.05) above basal at the 0.3 micrograms/kg X min dose, but not at the 0.03 or 0.1 micrograms/kg X min dosage levels. There were no changes in blood pressure or potassium during either the 10 or 200-meq Na+ studies. Thus, beta-endorphin stimulates aldosterone release in vivo. However, the underlying mechanisms are complex, since renin levels also increased. The data suggest that the early aldosterone rise may be secondary to an increase in renin release, but renin cannot account for the sustained postinfusion elevations of aldosterone.

Low plasma renin activity in diabetes. Relation to urine prostaglandin excretion.

Renal functional abnormalities, occurring before overt renal disease and possibly due to abnormal vascular control mechanisms, have been described in diabetes mellitus. We used intravenous (i.v.) furosemide, which stimulates renal prostaglandin (PG) synthesis and renin release, to compare these vasoactive systems in 14 diabetic and 23 normal control subjects. Using urine thromboxane B2 (TXB2) as an index of renal synthesis of the vasoconstrictor prostanoid TXA2, and urine 6keto-PGF1 alpha for the vasodilator PGI2, we found evidence of increased renal TXA2 synthesis in diabetic subjects in response to furosemide. The increased TXA2 synthesis did not occur at the expense of PGI2 synthesis, as urine 6keto-PGF1 alpha was not reduced. Increased TXB2 excretion in diabetic subjects was particularly marked in the first 10 min after i.v. furosemide. During this time, diabetic males excreted 31 +/- 6 ng of TXB2 compared with 10 +/- 1 ng for normal males (P less than 0.05), while diabetic females excreted 15 +/- 3 ng compared with 7 +/- 1 ng for normal females (P less than 0.05). Also, 6keto-PGF1 alpha excretion at 10 min was increased in diabetic subjects: males, 29 +/- 3 ng versus 19 +/- 3 (P less than 0.05); females, 33 +/- 8 versus 16 +/- 3 (P less than 0.05). The ratio of TXB2 to 6keto-PGF1 alpha tended to be higher in diabetic males.(ABSTRACT TRUNCATED AT 250 WORDS)

Activation of the Renin-Angiotensin System by Sodium Nitroprusside in Essential Hypertension

We previously have demonstrated that the sympathetic nervous system is activated proportionately to the degree of vasodepression induced in hypertensive patients. In the present study, the role of the renin-angiotensin system in modulating the vasodepressor response to sodium nitroprusside was examined. Nine hospitalized hypertensive patients receiving a diuretic were given serially incremental doses of sodium nitroprusside over a dose range of 0.05-4.8 micrograms/kg/min with each dose being infused for 10 min. Mean arterial pressure (MAP), heart rate (HR), plasma renin activity (PRA), and plasma norepinephrine (NE) concentration were measured prior to and during each dose level of sodium nitroprusside. Stepwise increments in PRA were seen in each patient as the dose of sodium nitroprusside was increased. The increase in PRA was proportional to the increase in plasma NE concentration and to the decrease in MAP in each patient. However, considerable intersubject variation was seen in these relationships. When examined by multiple linear stepwise regression analysis, the degree of vasodepression was found to be dependent on the baseline blood pressure and baroreflex sensitivity (r = 0.97). However, increment in PRA was not an independent determinant of the vasodepressor response. Thus, the renin angiotensin system may not be a significant component of the acute homeostatic response to vasodepression in these patients.

Mechanism of renin release in exercising dog.

Exercise is associated with an increase in plasma renin activity (PRA). The purpose of this study was to determine the role of the prostaglandin (PG) and adrenergic pathways in the renin release with exercise in the dog. One group of animals (n = 4) was exercised under control untreated and indomethacin- and meclofenamate- (2 mg/kg) treated conditions. A 155% increase in PRA was not influenced by PG inhibition. In a second group (n = 7) PRA was 1.22 +/- 0.32, 3.29 +/- 1.59, 6.28 +/- 2.85, and 5.30 +/- 2.00 ng ANG I X ml-1 X h-1 at rest and during light, moderate, and heavy exercise, respectively. Guanethidine treatment (15 mg/kg) decreased mean PRA by 41, 50, 70, and 73% at rest and during the three levels of exercise, respectively. In a third group (n = 5) control exercise runs were repeated after metoprolol treatment. Selective beta 1-blockade completely abolished the increment in PRA observed with exercise. These data demonstrate that the elevation of PRA during exercise in the dog is mediated by increased sympathetic nerve activity involving beta 1-receptors and that it is not dependent on alterations in PG synthesis.

Influence of augmented Hageman factor (Factor XII) titers on the cryoactivation of plasma prorenin in women using oral contraceptive agents.

Prolonged cold storage of plasma may induce the conversion of plasma prorenin (inactive renin) to renin. This phenomenon is exaggerated in oral contraceptive (OC) users; the titer of Hageman factor (HF, Factor XII) in OC users is higher than in nonusers. The present study relates these observations. The increment in plasma renin activity (PRA) during cold storage, as measured by generation of angiotensin I, correlated strongly with the initial plasma titer of HF. Increasing the HF titer of nonusers to that observed in OC users by addition of purified HF increased cold-induced PRA at least twofold, while reducing the plasma HF titer of OC users correspondingly decreased cold-induced PRA. Thus, in OC users, the enhanced conversion of plasma prorenin to renin during cold storage reflects the elevated plasma titer of HF.

Time course and effect of sodium intake on vascular and hormonal responses to enalapril (MK 421) in normal subjects.

Enalapril (MK 421) is a long-acting angiotensin converting-enzyme inhibitor which specifically lacks the sulfhydryl group of captopril. We measured arterial pressure and hormonal responses that occurred in 22 normotensive subjects treated with increasing doses of enalapril (2.5, 5, 10, and 20 mg) once daily, who were on either low (10 mEq) or high (200 mEq) sodium diets. In sodium-restricted subjects (n = 12), mean diastolic blood pressure declined from control levels in a dose-related fashion during the first 2 h. The mean 24-h diastolic blood pressure values were significantly lower than control (p less than 0.01) at all doses, with the greatest declines occurring with the 10 and 20 mg doses. Accompanying the decline in blood pressure was a significant increase in plasma renin activity (PRA) and reduction in plasma angiotensin II (AII) and aldosterone levels. As with blood pressure, the greatest changes were observed with the 5, 10, and 20 mg doses. However, only the 20 mg dose of enalapril produced prolonged and significant PRA increments (p less than 0.01) and AII decrements (p less than 0.05) of at least 24 h in duration. In sodium-replete subjects (n = 10), a similar pattern of diastolic blood pressure responses was observed; however, the effect of the drug was not so profound. No significant decrease in AII occurred at any dose of enalapril; however, PRA increased modestly but significantly (p less than 0.01) after administration of 5, 10, and 20 mg enalapril. Plasma aldosterone declined modestly but significantly, 2 (p less than 0.05) and 4 (p less than 0.01) h after the 10 mg dose.(ABSTRACT TRUNCATED AT 250 WORDS)