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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study, using non-invasive techniques, was carried out in ten patients with essential hypertension to examine the mechanism of the hypotensive effect of propranolol when used in combination with a potent vasodilator antihypertensive - minoxidil. The hypotensive effect of minoxidil, a mean (+/- SEM) decrease of 42.4 +/- 4.3 mm Hg, was accompanied by a marked increase in heart rate, cardiac index and plasma renin activity and a significant decrease in total peripheral resistance, limb vascular resistance and pre-ejection period. Addition of propranolol further reduced mean arterial pressure by an average of 12.9 +/- 2.0 mm Hg. Propranolol returned cardiac index to control values and total peripheral resistance index rose but not to control levels. Plasma renin activity was significantly reduced by propranolol. By multiple regression analysis no correlation was found between propranolol-induced decrease in mean arterial pressure and changes in cardiac index, total peripheral resistance index or plasma renin activity. Quantitatively, the reduction in cardiac index observed probably accounted for the hypotensive effect of propranolol. The role of plasma renin activity reduction in the hypotensive effect of propranolol in this situation remains to be clarified. The findings in the present study were consonant with the known actions of vasodilator antihypertensive agents and propranolol and indicate the applicability of non-invasive methodology to the investigation of cardiovascular drugs in man.
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PMID:Mechanism of the interaction of propranolol and a potent vasodilator antihypertensive agent - minoxidil. 97

Renin activities were determined in plasma and in single, microdissected juxtaglomerular apparatus in 19 patients with unilateral renal artery stenosis. The mean juxtaglomerular apparatus renin concentration in the stenosed kidneys was 5.5 +/- 1.2 (SEM) mug.l-1.h-1 which is about ten times that of the suppressed renin concentration in the contralateral kidneys (0.6 +/- 0.05 mug.l-1.h-1). On the affected side a positive correlation was found between intrarenal and renal venous renin concentration (r = 0.93; p less than 0.001). Both intrarenal and renal venous renin concentrations of the stenosed kindeys were positively correlated to renin secretion rates, as calculated from renin analysis in plasma from the vena cava and renal veins. No relationship could be demonstrated between intrarenal or renal venous renin concentration and the degree of blood pressure elevation or transstenotic pressure gradient. However, a positive correlation was evident between peripheral plasma renin activity and diastolic blood pressure (r = 0.88; p less than 0.001). Comparative enzyme kinetic analyses of renin from the juxtaglomerular apparatus and renal venous plasma were performed using sheep substrate. The lowest apparent Km-values of renin were found in renal venous plasma from the stenosed kidneys (198 +/- 13 mug/l) compared with the contralateral side (301 +/- 20 mug/l; p less than 0.001). Mean apparent Km-values of juxtaglomerular apparatus renin in the stenosed (270 +/- 36 mug/l) and contralateral (292 +/- 37 mug/l) kidneys did not differ. No significant differences were found between mean apparent Km-values for renin in peripheral plasma of renovascular hypertensive patients and control subjects using either homologous human or heterologous sheep renin substrate. The results suggest that, in addition to the renin concentration other factors are relevant to chronic high blood pressure in renovascular hypertension.
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PMID:Kidney and plasma renin in human renovascular hypertension. 100 43

The circadian rhythm of plasma renin activity during continuous recumbency was determined fifty-one times in thirty subjects who either slept at night or remained awake for 24 h. Both groups had maximum values between 2400 and 0800 h, despite absence of the expected early morning fall in blood pressure, pulse, and glomerular filtration rate in the awake subjects. Infusion of normal saline between 2300 and 0300 h initially suppressed renin, but did not prevent its subsequent rise regardless of the amount of sodium appearing in the urine. Of thirteen patients tested two to five times, twelve had recurrence of the zenith within a single 4 h period on retesting, despite differences in sodium intake, basal blood pressure, and mean plasma renin activity. Peaks of lesser magnitude were also frequently noted, most commonly at 1000 h and 1800-2000 h. Minimum PRA values were not restricted to a particular time of day and did not generally recur at the same time upon retesting. The mean ratio of maximum to minimum PRA in each study was 246% +/- 18.3% (+/- 1 SEM). The circadian rhythm of renin appears to be independent of known renal mechanisms responsible for regulating renin release. It is possible that this rhythm is controlled by the central nervous system.
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PMID:The circadian rhythm of renin. 100 16

1. Indomethacin inhibits prostaglandin synthesis and interferes with renin release; these effects were studied in rabbit renovascular hypertension. 2. Ten intravenous injections (3 mg day-1 kg-1 after two initial doses of 9 mg/kg) of indomethacin were given daily to ten normal rabbits, ten rabbits with two-kidney Goldblatt hypertension (2KH), tension (1KH). Twelve appropriate control rabbits received diluent phosphate buffer without indomethacin. Plasma renin activity and plasma prostaglandin E2 were measured by radioimmunoassay. 3. In the normal group, indomethacin significantly decreased plasma prostaglandin E2 (1-15 to 0-2 ng/ml, SEM 0-2; P less than 0-01) and plasma renin activity (20 to 3 ng h-1 ml-1, SEM 1, P less than 0-01). Plasma creatinine increased slightly but the mean blood pressure was not significantly changed by indomethacin. 4. Six of ten rabbits with 2KH showed results similar to those in the normal rabbits. In four of ten rabbits in which development of 2KH was accompanied by increments in plasma renin activity (18 to 31-5 ng h-1 ml-1, SEM 3 and 4 respectively; P less than 0-01) and plasma prostaglandin E2 (1-2 to 3-4 ng/ml, SEM 0-2 and 0-4 respectively; P less than 0-05), treatment with indomethacin produced renal failure (plasma creatinine increasing to 7-6 mg/100 ml), oliguria, malignant hypertension (mean blood pressure, 168 mmHg, SEM 7-7) and death within 5 days. 5. In 1KH, indomethacin decreased plasma renin activity and plasma prostaglandin E2, but caused increased mean blood pressure (102 to 121 mmHg, SEM 4 and 6 respectively; P less than 0-01) and decreased renal function (plasma creatinine 0-9 +/- 0-04 to 3-5 +/- 1 mg/100 ml, SEM 0-04 and 1 respectively; P less than 0-01). 6. Aggravation of hypertension was conditioned by pre-existing levels of renal function and, to a lesser extent, by plasma renin activities. 7. These results suggest that prostaglandins exert a protective effect on renal function in renovascular hypertension.
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PMID:Effects of indomethacin in rabbit renovascular hypertension. 107 20

A study was made of the possible mechanism(s) underlying minoxidil-induced increase in plasma renin activity (PRA). 10 patients with essential hypertension were treated with minoxidil and subsequently with a combination of minoxidil plus propranolol. Minoxidil lowered mean arterial pressure 31.6 plus or minus 3.3 mm Hg, mean plus or minus SEM. There was an associated increase in both PRA, 6.26 plus or minus 2.43 NG/ML/H, and heart rate, 21.4 plus or minus 2.7 beats/min. The changes in PRA and heart rate were positively correlated, r, 0.79. Addition of propranolol reduced mean arterial pressure by a further 10.1 plus or minus 1.5 mm Hg and returned heart rate to control levels. Propranolol reduced PRA significantly but not to control levels. Control PRA positively correlated with PRA on minoxidil, r, 0.97, and with PRA on minoxidil plus propranolol, r, 0.98. We conclude that control PRA is a major determinant of change in PRA with minoxidil. Minoxidil increased PRA by at least two mechanisms: (a) an adrenergic mechanism closely related to change in heart rate and blocked by propranolol, and (b) a mechanism(s) not sensitive to propranolol and possibly related to decrease in renal perfusion pressure.
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PMID:Control plasma renin activity and changes in sympathetic tone as determinants of minoxidil-induced increase in plasma renin activity. 112 99

Since previous studies from this laboratory have demonstrated that the redistribution of blood volume and concomitant relative central hypervolemia induced by water immersion to the neck causes a profound natriuresis and a suppression of the renin-aldosterone system, it was of interest to assess whether the diuresis induced by immersion was mediated by an analogous inhibition of ADH. The effects of water immersion on renal water handling and urinary ADH excretion were assessed in 10 normal male subjects studied following 14 h of overnight dehydration on two occasions, control and immersion. The conditions of seated posture and time of day were identical. During control ADH persisted at or above prestudy values. Immersion resulted in a progressive decrease in ADH excretion from 80.1 plus or minus 7 (SEM) to 37.3 plus or minus 6.3 muU/min (P smaller than 0.025). Cessation of immersion was associated with a marked increase in ADH from 37.3 +/- 6.3 muU/min to 176.6 +/- 72.6 muU/min during the recovery hour (P smaller than 0.05). Concomitant with these changes urine osmolality decreased significantly beginning as early as the initial hour of immersion from 1044 +/- 36 to 542 +/- 66 mosmol/kg H2O during the final hour of immersion (P smaller than 0.001). Recovery was associated with a significant mean increase in Uosm of 190 +/- 40 mosmol/kg H2O over the final hour of immersion (P smaller than 0.001). The suppression of ADH occurred without concomitant changes in plasma tonicity. These studies are consistent with the suggestion that in hydrated subjects undergoing immersion suppression of ADH release contributes to the enhanced free water clearance, which has been previously documented.
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PMID:Suppression of ADH during water immersion in normal man. 114 Nov 16

Ethacrynic acid infused i.v. in anesthetized dogs after inhibiting sympathetic mechanisms of renin release increased renal blood flow rate (RBF) by 54% and practically abolished autoregulation of RBF; renin release increased from 0.8 +/- 0.9 (mean +/- SEM) to 16.4 +/- 3.7 mug/min (P less than 0.05). Without infusion of ethacrynic acid; constriction of the renal artery to a pressure below the range of autoregulation reduced renovascular resistance markedly and renin release rose to 27.2 +/- 5.5 mug/min (P less than 0.05). During arterial constriction, ethacrynic acid had no additional effect on renovascular resistance or renin release averaging 28.4 +/- 6.7 mug/min. Infusion of ethacrynic acid and saline at control pressure increased sodium excretion to about one-half of the filtrate and reduced rein release which did not, however, return to control. Infusion of hypertonic saline during autoregulated vasodilatation induced by arterial constriction had a similar effect, but again renin release continued to exceed control. We propose that ethacrynic acid increases renin release through a hemodynamic mechanism triggered by afferent arteriolar dilation and inhibits renin release by greatly increasing the delivery of sodium to the distal convoluted tubules.
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PMID:Influence of ethacrynic acid on intrarenal renin release mechanisms. 117 75

In 19 control subjects, 33 patients with essential hypertension and normal plasma renin activity (PRA) and 11 patients with low PRA, secretory rates of 18-hydroxy-11-deoxy-corticosterone (18-OH DOC), 11-deoxycorticosterone (DOC) and corticosterone were measured. Patients with low PRA were significantly older and had higher arterial pressure and slightly lower plasma potassium levels than patients with normal PRA. Mean 18-OH DOC secretion rate was higher in patients with normal PRA (603 +/- 112 SEM mug/24 hr) than in control subjects (219 +/- 19) and considerably higher (P less than 0.001) in patients with low PRA (1800 +/- 472). DOC and corticosterone secretion rates were within normal limits in most hypertensive patients. Plasma aldosterone was significantly higher in the hypertensive population than in control subjects whereas no significant difference was observed between the low- and normal-renin groups. A significant (P less than 0.01) mutual positive correlation was found between the secretion rates of 18-OH DOC, DOC and corticosterone in patients with low plasma renin activity. In contrast, there was no correlation between the secretion rates of the three mineralocorticoids in control subjects and patients with normal plasma renin activity. These data suggest a biosynthetic variation of the mineralocorticoid pathways in essential hypertension.
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PMID:Mineralocorticoid secretion in essential hypertension with normal and low plasma renin activity. 124 73

1. This study in conscious dogs examined the quantitative effects of a reduction in the renal arterial pressure on the renal homeostatic responses to an acute extracellular fluid volume expansion. 2. Seven female beagle dogs were chronically instrumented with two aortic catheters, one central venous catheter and a suprarenal aortic cuff, and were kept under standardized conditions on a constant high dietary sodium intake (14.5 mmol of Na+ day-1 kg-1 body weight). 3. After a 60 min control period, 0.9% (w/v) NaCl was infused at a rate of 1 ml min-1 kg-1 body weight for 60 min (infusion period). Two different protocols were applied during the infusion period: renal arterial pressure was maintained at 102 +/- 1 mmHg by means of a servo-feedback control circuit (RAP-sc, 14 experiments) or was left free (RAP-f, 14 experiments). 4. During the infusion period, in the RAP-sc protocol as well as in the RAP-f protocol, the mean arterial pressure increased by 10 mmHg, the heart rate increased by 20 beats/min, the central venous pressure increased by 4 cmH2O and the glomerular filtration rate (control 5.1 +/- 0.3 ml min-1 kg-1 body weight, mean +/- SEM) increased by 1 ml min-1 kg-1. 5. Plasma renin activity [control 0.85 +/- 0.15 (RAP-f) and 1.08 +/- 0.23 (RAP-sc) pmol of angiotensin I h-1 ml-1] decreased similarly in both protocols.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of renal arterial pressure in the regulation of extracellular volume in conscious dogs. 131 8

To elucidate the mechanism of hyperkalemia in diabetic patients without renal failure, we investigated (Na(+)-K+) adenosine triphosphatase (ATPase) activity in erythrocyte membrane, erythrocyte Na+ and K+ content, and plasma endogenous digitalis-like substance in control subjects (n = 16) and non-insulin-dependent diabetes mellitus (NIDDM) patients (n = 62). NIDDM patients were divided into normokalemic patients (NKDM, n = 48) and hyperkalemic patients (HKDM, n = 14). There was no difference in plasma glucose or hemoglobin A1c (HbA1c) levels, plasma renin activity (PRA), and plasma aldosterone concentrations (PAC) between NKDM and HKDM patients. (Na(+)-K+)ATPase activities in NIDDM patients were significantly reduced compared with those in control subjects (0.336 +/- 0.016 mumol-inorganic phosphate [Pi]/mg protein/h, mean +/- SEM, P less than .05), and (Na(+)-K+)ATPase activities in HKDM patients (0.243 +/- 0.015 mumol Pi/mg protein/h) were significantly reduced compared with those in NKDM patients (0.295 +/- 0.008 mumol Pi/mg protein/h, P less than .01). Plasma K+ content had a significant negative correlation with (Na(+)-K+)ATPase activity in diabetic patients (r = -.365, P less than .01). Erythrocyte Na+ content had a significant negative correlation with (Na(+)-K+)ATPase activity in control subjects (r = -.619, P less than .05). There was no difference in plasma endogenous digitalis-like substance among the three groups. (Na(+)-K+)ATPase activity was not significantly correlated with plasma endogenous digitalis-like substance in control subjects and diabetic patients. These findings suggest that the reduction of (Na(+)-K+)ATPase activity, which was not related to plasma digitalis-like substance, may be partly responsible for hyperkalemia in diabetic patients.
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PMID:Reduction of erythrocyte (Na(+)-K+) ATPase activities in non-insulin-dependent diabetic patients with hyperkalemia. 131 28


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