Fall In Plasma Renin Concentration Research Articles

Aldosterone-to-renin ratio depends on age and sex in children attending a clinic for cardiovascular risk assessment

To determine plasma aldosterone concentration (PAC) and plasma renin concentration (PRC) and aldosterone-to-renin ratio (ARR) values in a population attending a Clinic for Cardiovascular Risk Assessment in Children. We assessed ARR and associated factors in a cohort of 287 children (137 female, 4-18 years). Weight and blood pressure (BP) were recorded. PAC (ng/dl) and PRC (mU/l) were measured using direct immunochemiluminescent assays. Data were examined by sex and according to four age classes. Median PAC was similar from the youngest to the oldest age class ranging from 7.5 to 9.9 ng/dl in males and from 11.0 to 12.6 ng/dl in females. Median PRC was also similar across age classes in males ranging from 58.2 to 55.5 mU/l, whereas it progressively decreased from 61.5 to 36.6 mU/l in females (P < 0.01). Median PRC was higher in prepubertal than in pubertal females only (53.6 vs. 40.2 mU/l, P < 0.03). As a result ARR was unchanged with increasing age in males (from 0.18 to 0.19), whereas in females it increased from 0.19 to 0.36 (P < 0.03). After adjusting for body weight, BP and other possible confounders, age was inversely related with PRC and directly with PAC and ARR (P < 0.001 for all), in females only. No relationship was found in both sexes between ARR values, BP, weight and family history of hypertension. In our children population, ARR is lower than in adults and diverges with increasing age between sexes, due to the age and puberty driven fall in PRC observed only in females. BP and weight are not associated with ARR distribution.

Down-regulation of the intrarenal renin-angiotensin system in the aging rat.

Progressive deterioration of renal function occurs during normal aging. Previous studies on the aging kidney have demonstrated glomerular hemodynamic changes, specifically, glomerular capillary hypertension, as maladaptations that lead to proteinuria and glomerular sclerosis over time. Aging rats treated with angiotensin-converting enzyme inhibition have relatively less proteinuria and sclerosis, suggesting that age-related changes in renal function may be associated with alterations in the intrarenal renin-angiotensin system, which thus may play a major role in the pathogenesis of these maladaptations. To investigate this possibility, renal and systemic renin-angiotensin systems were examined at an early phase of the aging process (3 months) and at a later phase (12 months) in male Sprague-Dawley rats. Although plasma renin and serum angiotensin-converting enzyme concentrations did not differ significantly, the intrarenal system showed down-regulation of renin mRNA and angiotensin-converting enzyme levels with aging, whereas angiotensinogen levels remained stable. The decrease in renin mRNA appeared to precede the fall in plasma renin concentration in the aging process. Additional studies in 15-month-old rats confirmed that, by this time, both basal and stimulated renal renin release rates were impaired in older rats. Thus, both decreased renin synthesis and impaired renin release underlie the fall in plasma renin with normal aging. This decrease may act to lower intrarenal baseline levels of angiotensin II, an adaptation of likely importance in the modulation of intrarenal vascular tone and tubular function in the aging kidney.

Propranolol and atenolol inhibit norepinephrine spillover rate into plasma in conscious spontaneously hypertensive rats

Radiotracer techniques capable of measuring norepinephrine clearance and spillover rate into plasma were used to test the hypothesis that the antihypertensive effects of propranolol and atenolol in conscious spontaneously hypertensive rats are associated with an inhibition of norepinephrine release from postganglionic sympathetic neurons. The 10%-15% fall in mean arterial pressure produced over 4 h by propranolol (1, 3.3 and 10 mg/kg, s.c.) and atenolol (1, 3.3 and 10 mg/kg, s.c.) was not dose-related, and only the largest dose of propranolol caused a significant bradycardia. Each dose of atenolol significantly lowered heart rate. The decrease in blood pressure caused by propranolol and atenolol was not related to the decrease in heart rate. Both propranolol and atenolol inhibited norepinephrine clearance by 12% to 16%. The 1 mg/kg doses of propranolol and atenolol significantly suppressed norepinephrine spillover rate by 21% and 32%, respectively, at 4 h postinjection. As the dose of propranolol was increased, the inhibition of norepinephrine spillover was reversed as plasma epinephrine concentration rose by 125%. The suppression of norepinephrine spillover rate caused by atenolol was more persistent but did diminish after the 10 mg/kg dose, when plasma epinephrine concentration was elevated by 55%. Both drugs suppressed plasma renin concentration, but the inhibition of norepinephrine spillover rate by propranolol and atenolol was not related to the fall in plasma renin concentration. By comparison, treatment with the adrenergic neuron blocking agent bretylium (5, 10, 20 and 40 mg/kg, s.c.) elicited a dose-related vasodepression with no change in heart rate or plasma renin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrastructural changes in the sheep renal juxtaglomerular apparatus in response to sodium depletion or loading

The ultrastructural changes in various components of the renal juxtaglomerular apparatus have been examined in sheep subjected to sodium depletion or loading. In normal sheep, juxtaglomerular arteriolar myoepithelioid cell granulation was relatively sparse whereas peripolar cell granulation was prominent. Sheep subjected to rapid sodium depletion in response to parotid cannula drainage showed features indicating increased activity of the renin-angiotensin system with a rise in plasma renin concentration, an increase in the juxtaglomerular index and morphological evidence of increased renin granule production in arteriolar myoepithelioid cells. In contrast, in sheep subjected to dietary sodium loading, there was evidence of decreased activity of the renin-angiotensin system with a fall in plasma renin concentration and relatively poor myoepithelioid cell granulation. In sodium depleted sheep, juxtaglomerular peripolar cells showed increased synthetic activity and marked heterogeneity of granule density; in sodium loaded sheep, peripolar cells showed no consistent changes. A major new finding was the detection of exocytotic release of granule material from peripolar cells into the urinary space during sodium depletion, confirming the secretory nature of such cells and supporting the concept that they may play a role in sodium homeostasis.

Effect of Sotalol on Haemodynamics and Renin—Angiotensin—Aldosterone System in Hypertensive Patients

1. Twenty-three hypertensive patients were treated by sotalol, a pure beta-adrenergic receptor blocking agent. The drug produced a significant decrease of blood pressure in nineteen patients. 2. On average, cardiac index decreased but not significantly; heart rate decreased and stroke index increased significantly. Total peripheral resistance varied in both directions. 3. Sotalol determined a fall in plasma renin concentration (only significant in the high-renin group), a fall in plasma angiotensin II concentration and in urinary excretion rate of aldosterone accompanied by a rise in plasma potassium concentration. 4. The fall of blood pressure was not correlated with the decreases of renin and angiotensin II concentrations or excretion rate of aldosterone. However, in the placebo period plasma angiotensin II concentration was significantly correlated with total peripheral resistance; during sotalol treatment the variations of these two parameters seemed also to be correlated. 5. There was a poor correlation between decreases of cardiac output and of blood pressure; it was impossible to foresee the magnitude of the lowering of the blood pressure from the initial cardiac index. 6. The association of a diuretic with sotalol enhanced the hypotensive effect of the beta-receptor blocking drug, without significant increase of plasma renin and angiotensin II concentrations.

Drug-Induced Hypertension

PIP: Estrogenic compounds are the most important group of drugs that can induce hypertension. Studies have shown an incidence of significant hypertension amounting to less than 1% after 1 year of taking oral contraceptives and about 2% after 5 years. The ratio of the incidence of hypertension among ''takers'' to that of ''nontakers'' has been assessed at 1.8 by 1 study and 2.6 by another. Small but significant increments in systolic and diastolic pressures can be discerned during the first 2 years of treatment. Cessation of treatment has resulted in pressures returing to pretreatment levels within 3 months. In those previously normal the highest readings during oral contraceptive use were only 155/90 mm of Hg. Severe hypertension is more likely to occur in the predisposed, and malignant hypertension has been reported. Previous hypertension, toxemia of pregnancy, obesity, and nephropathy are predisposing conditions. Although progestagens, used alone, do not cause clinical hypertension the incidence of hypertension associated with an estrogen-progestogen combination was directly related to the dose of progestagen used. Weight gain is often observed in oral contraceptive users and is occasionally accompanied by edema and hypertension. There is a marked increase in the circulating level of renin substrate (angiotensinogen) which is caused by the estrogen component of the pill. The increase in renin substrate is associated with increase in plasma levels of renin activity, angiotensin 2, and aldosterone, together with a fall in plasma renin concentration. The suppression of plasma renin concentration can persist for weeks after stopping the pill. The factors responsible for hypertension are probably intrinsic and may be either neural, vascular, or renal. Patients taking oral contraceptives should have blood pressure checks at 6-month intervals, and more frequently in high risk cases. In the management of those with only mild blood pressure elevation, such patients should change to a preparation with the lowest available estrogen dosage, 30 mcg of ethinyl estradiol, or reserve the method for use during crucial periods of family planning. With moderate hypertension the oral contraceptive should be suspended for 3-6 months. If the blood pressure falls, oral contraceptives should not be resumed but another method recommended. Continuing hypertension requires further study and possibly elective sterilization. Severe hypertension requires withdrawal of the pill, urgent investigation, and treatment. Other drugs may cause hypertension. Management of these patients is outlined. Structural formulae of progesterone, norethisterone acetate, medroxyprogesterone acetate, and norgestrel are shown.

Effect of methylprednisolone upon arterial pressure and the renin angiotensin system in the rat

The effect of methylprednisolone or deoxycorticosterone upon systemic arterial blood pressure and components of the renin-angiotensin system was studied in the rat. Rats maintained on regular diets given methylprednisolone suspension 20 mg/kg body wt demonstrated a significant increase in arterial pressure of + 37 plus or minus 5 mmHg, mean plus or minus SE, over a 2-wk period, whereas those treated with DOC and untreated controls showed no significant change. On normal diets, plasma renin concentration (PRC) of methylprednisolone-treated rats was significantly higher than that of DOC-treated rats. Methylprednisolone treatment also resulted in a significant elevation of plasma renin substrate concentration (PRS). Calculated plasma renin activity (PRA) was highest in methylprednisolone-treated rats, significantly above that of the DOC and no-steroid groups. NaCl supplementation resulted in a significant fall in PRC and PRA in all three groups; however, PRS remained significantly above normal in the methylprednisolone-treated rats. The pressor effect of angiotensin II was slightly increased in methylprednisolone-treated rats. Infusion of [Sar1,Ala8]angiotensin II (P-113) in methylprednisolone-treated rats resulted in a significant fall in diastolic arterial pressure. The results imply that methylprednisolone hypertension in the rat may be in part angiotensin dependent.

Effect of alprenolol and hydralazine on plasma renin concentration in patients with arterial hypertension.

The effect of alprenolol alone and in combination with hydralazine on plasma renin concentration has been studied in 25 patients with arterial hypertension. Alprenolol caused a significant fall in plasma renin concentration and in BP but the two falls were not intercorrelated. Addition of hydralazine to the treatment regimen produced a further reduction of BP. Changes in plasma renin concentration varied greatly during combination therapy. A modest, non-significant increase in plasma renin concentration was measured compared with the level after treatment with alprenolol. It is concluded that mechanisms other than suppression of plasma renin concentration are important for the reduction of BP during beta-adrenergic blockade and that the plasma renin concentration probably has no clinical significance with regard to forecasting the antihypertensive effect of alprenolol. Even though a significant correlation was found between the fall in plasma renin concentration and the fall in diastolic BP during combination therapy, it is uncertain whether changes in the renin-angiotensin system are of primary importance for BP regulation during this therapy.

Antidiuretic hormone and renin in rats with diabetes insipidus

Administration of antidiuretic hormone to rats at a dose of 400 or 40 mu/100 g i.m. caused a significant fall in plasma renin concentration. (PRC). In male rats with diabetes insipidus, a significant elevation of both plasma and kidney renin concentrations was not significantly different from that in control female rats. Ovariectomy did not abolish this difference between female and male rats with hereditary diabetes insipidus. Plasma angiotensinogen (renin substrate) was significantly higher in male rats compared to females but no difference between rats with and without diabetes insipidus was observed.

The clearance of endogenous renin in the anhepatic anephric dog.

1. A rapid fall in plasma renin concentration occurs not only in colonectomized but also in hepatectomized dogs after binephrectomy. 2. In the anhepatic anephric dog no renin extraction can be demonstrated across lungs, splanchnic region, spleen, inferior limb and head. 3. No renin inactivation occurs in blood kept in vitro at 37°C for 3 h taken from anaesthetized dogs and from the anhepatic anephric dogs. 4. We suggest that the clearance of renin in the anhepatic anephric dog is due to extraction or inactivation of renin by tissues in general.

Cellophane perinephritis hypertension and its reversal in rabbits. Effect on plasma renin, renin substrate, and renal mass.

Plasma renin activity and renin substrate levels were measured during the development of cellophane perinephritis hypertension induced by either a bilateral renal wrap procedure or a wrap-nephrectomy procedure in 28 rabbits. Unoperated and unilaterally nephrectomized controls were also studied. Plasma renin concentration was derived from plasma renin activity and plasma renin substrate levels using a measured K m of 2.3 x 10 -6 M. All surgical operations were followed by a transient increase in plasma renin substrate levels and a fall in plasma renin concentration. Unilateral nephrectomy in normotensive controls suppressed plasma renin activity and concentration for a 20-day period. Similar suppression occurred during the onset of hypertension in rabbits subjected to the wrap-nephrectomy procedure. Decapsulation accompanied by a fall in blood pressure again suppressed plasma renin activity and concentration. With bilateral wrapping, hypertension developed gradually without a change in renin levels. Decreased renin secretion during the evolution of perinephritis hypertension probably reflects a decreased renal excretory capacity for salt and water that overrides the renin-releasing effect of renal compression.

The natriuresis of fasting: relationship to changes in plasma renin and plasma aldosterone concentrations.

1. The relationship of changes in plasma renin and plasma aldosterone concentration to electrolyte balance was studied during total fasting and during sodium deprivation followed by total fasting. 2. During simple sodium deprivation obese subjects lost significantly more sodium than lean subjects, but the rise in plasma renin concentration (PRC) was similar in the two groups. 3. During total fasting there was a failure of PRC to increase in the expected manner despite a marked negative sodium balance. In the early stages of the fast, PRC decreased in nine of eleven subjects while subsequently it increased in all subjects. 4. During sodium deprivation PRC and plasma aldosterone concentration (PAC) rose in all subjects studied, but in the first few days of a period of total fasting immediately following, there was a fall in PRC in eight of ten subjects studied, while PAC continued to rise in five of six subjects in whom it was measured. 5. These results are discussed in relation to the concept of the renin-angiotensin system as a regulator of aldosterone secretion.