THE EFFECTS OF INTRAVENOUS INFUSIONS OF VALINE-5 ANGIOTENSIN II AND OTHER PRESSOR AGENTS ON URINARY ELECTROLYTES AND CORTICOSTEROIDS, INCLUDING ALDOSTERONE*

Abstract

Previous studies from this laboratory (1-4) have shown that: 1) there is a statistically significant increase in the mean urinary aldosterone excretion from groups of patients with essential, renal or malignant hypertension, as compared with that of normal subjects similarly studied; 2) 43 per cent of patients with essential hypertension have urinary aldosterone values above normal limits; 3) there is an excessive fluctuation of daily urinary aldosterone in hypertensive patients, from normal to above normal levels, which is most prominent in the early phase of the disease; and 4) mean urinary preglnanetriol is significantly decreased (p < 0.001) in the same groups of hyper-tensive patients, and the pregnanetriol/aldosterone ratio is below the lower limits of normal range in 92 per cent of all patients studied with arterial hypertension. The findings of a mean increase in urinary aldo-sterone and of its excessive daily fluctuation in hypertensive patients have recently been confirmed by Romanelli, Biancalona and Matterazzi (5), Ven-ning, Dyrenfurth, Dossetor and Beck (6) and Schwartz (7). However, Laragh and co-workers (8), using a method devised by Ulick, Laragh and Lieberman (9) for the measurement of aldoster-one secretion rate, found normal values in 8 patients with benign essential hypertension and significantly increased secretion rates in 5 of 8 patients with advanced hypertension and in 14 of 15 patients with malignant hypertension. On the other hand, in a preliminary study, Muller found normal aldosterone secretion rates in patients with malignant hypertension (10). It appears however, that this disturbance in adrenocortical regulation may not be the basic or the sole factor in the pathogenesis of hypertension. Both clinical and experimental evidence strongly suggest that the kidney plays a definite role. We therefore studied the possibility of a relationship between the renal pressor system and aldosterone. Our preliminary results (11), showing a marked stimulatory effect of angiotensin II on urinary aldosteronie, have been confirmed in the present study. Seven normal subjects were studied. Continuous intravenous infusions of glucose, angio-tensin, norepinephrine and phenylephrine were administered for periods of 7 to 14 hours, and urines were analyzed for sodium, potassium, aldo-sterone, cortisol, cortisone and their tetrahydro derivatives. The results obtained show a marked and specific tropic effect of angiotensin on aldo-sterone excretion. SUBJECTS AND METHODS The subjects were 7 healthy male volunteer medical students, maintained on a fixed sodium and potassium intake (102 and 90 mEq per day, respectively) for 5 days prior to and during the experimental period. They were admitted to hospital for metabolic balance for the duration of the experiments. Urine was collected every 24 hours, except on infusion days, when it was collected during the period of infusion and again separately for the rest of the 24 hour period (post-infusion period). Six infusions were carried out with synthetic valine-5 angiotensin II, two with norepinephrine 1 and two with phenyleph-rine.2 The pressor substances were diluted in 5 per cent Winthrop, Levophed. 2Winthrop, Neosynephrine. 338