Ageing and circadian rhythm of plasma renin and aldosterone.

Five men and 8 women, 60-69 yr of age, and 4 men and 5 women, 17-37 yr of age, volunteered for this exploration of possible age-related changes in circadian-rhythm (CR) characteristics of radioimmunoassayable plasma renin (PRA) and aldosterone (PA). Blood was drawn at 06.00, 08.00, 12.00, 18.00, 20.00 and 24.00 from recumbent subjects on a habitual sodium intake of 120-140 mEq/24 h. Time-qualified data of PRA and PA, fitted by a 24-h cosine curve, were summarized by a population mean-cosinor method. Circadian characteristics were compared by a multivariate analysis using Hotelling's t2 test. Rhythmometry reveals in the elderly women a lower mesor (P less than 0.001) and amplitude (P = 0.036) of the CR in PRA and a higher mesor and amplitude (P = 0.021 and P = 0.020, respectively) of the PA-CR. The PRA acrophase is delayed (P less than 0.001) in the elderly women (04.40 vs. 08.04) while the timing of the PA acrophase is similar in the age groups of women compared (05.52 vs. 05.20). These differences found in women were not observed in the smaller groups of men. The seventh decade of life may be characterized by an internal circadian desynchronization between the major components of the renin-angiotensin-aldosterone system. A sex-dependent amplification of the extent of circadian variation in aldosterone may precede a decrease in the circadian amplitude occurring during the eighth decade of life, as a sign of the adrenopause in women.

Circadian rhythms of plasma renin, aldosterone and cortisol on habitual and low dietary sodium intake.

To examine the effects of reducing sodium intake upon the renin-angiotensin-aldosterone system (RAAS), 5 healthy men and 5 healthy women, 17-37 years old, living under standardized conditions, were sampled around the clock, once on habitual and once on restricted sodium intake. Plasma renin activity (PRA), aldosterone (PA) and cortisol (PC) were determined by radioimmunoassay. All three variables were found to exhibit a statistically significant circadian rhythm, both on habitual and restricted salt intake. After salt restriction, an increase in midline-estimating statistic of rhythm (mesor) of PRA and PA, but not of PC, was observed. The acrophase (an estimate of the time of high values) for PC lagged behind that for PRA and PA. This difference in acrophase was of specially high statistical significance when subjects were on a sodium-restricted diet. These results demonstrate the importance of inferential statistical so-called rhythmometric methods: parameters such as the acrophase can also be used for the assessment of novel effects and for a quantification in time. The derivation of confidence intervals for each rhythm parameter allows one to verify that a given variable exhibits values bracketing an average not only between a higher and a lower, but also between an earlier and a later limit. Changes that may involve only the acrophase, such as a lead or lag, as here noted, are then detected and are of factual as well as methodological interest.

Renal-portal shunt to restore normal reninism and blood pressure in experimental renovascular hypertension in dogs.

The role of the liver in the metabolism of renin was evaluated in dogs with high plasma renin and hypertension due to experimental bilateral renal artery stenosis. Ten adult dogs were studied in three consecutive phases: (1) basal conditions, (2) with bilateral ischemic kidneys, and (3) after derivation of renal vein blood into the portal system. Secretion, total clearance, hepatic clearance, and hapatic extraction of renin were estimated in each phase by measuring plasma renin activity (PRA) in blood collected simultaneously from arteries, inferior vena cava, vena porta, hepatic and renal veins, and by determining renal and hepatic blood flow. Blood pressure was measured by intra-arterial catheterization. The results demonstrated an increase in the hepatic metabolism of renin when the hyper-reninemic patterns of renal blood directly perfused the liver. Under these conditions, hepatic and circulating renin fell to basal values and blood pressure returned to normal.

Rhythm characteristics of plasma renin, aldosterone and cortisol in five subtypes of mesor-hypertension.

The possible role of the renin-angiotensin system and ACTH in controlling the temporal organization of circadian rhythm of aldosterone was studied in patients with mesor-hypertension (MH) by simultaneous radioimmunological determinations of within-day changes in plasma renin, aldosterone and cortisol. Thirty-nine uncomplicated, untreated mesor-hypertensive patients, divided in subtypes, were examined. The interrelationship between the rhythm components revealed that the circadian cyclicity of aldosterone in both mesor-normotensive and mesor-hypertensive subjects, with either normal or high renin patterns, has a similar timing in acrophase with renin periodicity, which leads the circadian cortisol rhythm. In low-renin mesorhypertensive subjects a circadian rhythm of aldosterone and cortisol, but not of renin, remains demonstrable. The confidence limits of the estimated acrophase for circadian cortisol rhythm do not, however, overlap the confidence arcs of the aldosterone phase. These findings suggest that in normal or high renin MH subjects the aldosterone rhythmicity is mainly controlled by the renin-angiotensin system. Conversely in low-renin MH subjects the temporal organization of the aldosterone circadian sequences seems to be completely independent of renin-angiotensin control.

Beta-adrenergic regulation of circadian rhythmicity of the renin-angiotensin-aldosterone system in five subtypes of essential hypertension.

The possible implication of the beta-sympathoadrenergic system in regulating the rhythmicity of the renin-angiotensin-aldosterone system (RAAS) was studied in ten normotensive volunteers and in thirty-nine essential hypertensive patients. The study was carried out by simultaneous radioimmunological measurements of diurnal levels of plasma renin and aldosterone before and during acute oral medication of beta-adrenoceptors with propranolol. Acute beta-blockade was seen to blunt the circadian periodicity of plasma renin and aldosterone in normotensives and in hypertensives with normal or high renin patterns. Conversely propranolol was seen to be ineffective in low-renin patients. The disappearance of the circadian rhythms under beta-adrenoceptor blockade tends to suggest the existence of a beta-adrenergic control of RAAS cyclicity in normal condition, as well as in normal or high renin essential hypertension. The inefficacy of propranolol in hyporeninemic hypertensives is consistent with the hypothesis that low-renin essemtoa; juertemsopm os a state in which the sympatho beta-adrenergic mechanism controlling the function of RAAS has no biologic time structure.

[Temporal aspects of the function of the renin-angiotensin-aldosterone system. Contribution to the methodological standardization of explorative test (author's transl)]. / Aspetti temporali della dinamica del sistema renina-angiotensina-aldosterone. Contributo alla standardizzazione della metodologia di esplorazione funzionale.

The purpose of this study is to throw further light on the problem of the methodological standardization in the study of the renin-angiotensin-aldosterone system (RAAS). Thus, in 10 normal volunteers and 33 patients with moderate, recent and uncomplicated essential hypertension, divided into the subtypes with normal, high and low renin, it has been performed a timing analysis of the behaviour of plasma renin (PRA) and aldosterone (PA). PRA and PA were measured by radioimmunological methods in blood samples simultaneously collected in steady state conditions (study of circadian rhythmicity) and during the course of manipulative tests (orthostatism, dietary sodium restriction, orthostatism associated with sodium restriction, furosemide administration). The study revealed that each category of the present series of healthy and hypertensive individuals has an own temporal organization in the entire function of RAAS. This finding allowed to standardize the RIA reference indices as chronocorrelated intervals of normality and to establish the optimal criteria for the assessment of biochemical data and methodological study of hypertensive patients.