A. J. Dowdy

Abnormally sustained aldosterone secretion during salt loading in patients with various forms of benign hypertension; relation to plasma renin activity

Among 25 patients with benign, essential hypertension, and an equal number with other benign forms of hypertension, without serious cardiac, renal, or cerebrovascular impairment, 41 cases failed to reduce aldosterone excretion rates into the normal range (less than 5 mug/day) on a daily intake of 300 mEq of sodium. The hypertensive patients excreted slightly less than the normal fraction of labeled aldosterone as acid-hydrolyzable conjugate. Secretion rates were significantly higher in the hypertensive patients than in normotensive controls taking the high-sodium intake. On a 10 mEq sodium intake, the increase in excretion and secretion rates of aldosterone in the hypertensive patients could be correlated with plasma renin activity (PRA). The patients with the least increase in PRA had subnormal increase in aldosterone secretion and excretion, while unusually large rises in aldosterone secretion accompanied high PRA, especially in the cases with increased plasma angiotensinogen induced by oral contraceptives. The persistence of inappropriately high aldosterone secretion in most hypertensive patients during sodium loading could be related to a higher PRA than that found in normotensive controls under comparable conditions. In other hypertensives, whose PRA was unresponsive to sodium depletion, there was no significant correlation between PRA and aldosterone output, and no known stimulus to aldosterone production was detected. Five obvious cases of hyperaldosteronism were found among the 16 low-renin patients. The cause of the nonsuppressible aldosterone production in the other low-renin cases remains to be determined.

Hypertension induced by oral contraceptives containing estrogen and gestagen: effects on plasma renin activity and aldosterone excretion.

16 patients out of 53 referred for hypertension were taking oral contraceptives at the time of referral and were studied for blood pressure differentials plasma angiotensinogen levels plasma renin activity (PRA) and aldosterone excretion rates (AER) after cessation of the contraceptive treatment. Of the 11 patients who had normal blood pressure before taking the estrogen-gestagen contraceptives all of them showed reduced blood pressure levels within 1-3 months of stopping the treatment. 5 returned to and maintained normal limits for 6 months or longer while the remaining 6 showed reduced blood pressure levels that remained above the upper normal limits. In the 3 women who were hypertensive before treatment blood pressure fell to control levels after discontinuation. Angiotensinogen (renin substrate) concentration in the plasma of the patients receiving oral contraceptives was 2-5 times normal concentration. This also caused increase in angiotensinogen generation. These levels returned to normal within 3 months of cessation of contraception. PRA and AER were 2 times the normal rates under contraceptive therapy. PRA decreased but remained high in some cases 3 months after the treatment was stopped while AER returned to normal within the same period. It is concluded that oral contraceptives can cause hypertension in some patients and aggravate a pre-existing condition in others. Blood pressure therefore should be followed carefully in patients receiving oral contraceptives.

Decreased Plasma Clearance and Hepatic Extraction of Aldosterone in Patients with Heart Failure

Inexperimental congestive heart failure indogs, thesecretion rateofaldosterone ismarkedly elevated (1).Ayersandhiscolleagues (2)demonstrated adecreased rateofaldosterone removal fromplasma, whichresults inafurther increase in circulating aldosterone indogswithpassive congestion oftheliver. Yates, Urquhart, andHerbst (3)showed thatconstriction oftheinferior vena cavaabove thehepatic veins lowers theA&-steroid reductase activity ofliver homogenates inrats. Increased levels ofsodium-retaining steroids can becorrelated withreduced renal excretion ofsodiumandwiththecollection ofascites indogs after stenosis ofthepulmonic valve orconstriction oftheinferior venacava(4,5).

Distribution, conjugation, and excretion of labeled aldosterone in congestive heart failure and in controls with normal circulation: development and testing of a model with an analog computer.

The distribution and clearance of aldosterone from plasma determine the fraction of secreted hormone reaching sites where the cellular actions of the hormone occur. Tait, Tait, Little, and Laumas (1) described the disappearance of aldosterone from plasma of normal man in terms of a two compartment system. Davis, Olichney, Brown, and Binnion (2) showed that the volumes of distribution and rates of clearance of aldosterone are reduced in dogs with experimental heart failure and low cardiac output. Our findings indicate that marked alterations in distribution and clearance of aldosterone are present in patients with congestive failure. Tait, Little, Tait, and Flood (3) estimated the mean plasma concentration of aldosterone in human plasma from the secretion rate and the plasma clearance rate. Ayers and his colleagues (4) and Tait and associates (5) showed that hepatic clearance of aldosterone is subnormal in dogs or in man in congestive failure (4). Camargo, Dowdy, Hancock, and Luetscher (6) demonstrated that reduced hepatic clearance and extraction of aldosterone may contribute to an increased concentration in plasma of patients with heart failure. The liver extracts aldosterone from plasma and returns conjugates and metabolites to plasma, in

Observations on Metabolism of Aldosterone in Man

Excerpt In the evaluation of adrenal cortical function by laboratory tests, the essential diagnostic data are the concentrations of hormones in plasma or their metabolites in urine. After a baselin...

Clinical Course and Laboratory Data in Hypertension Associated with Oral Contraceptives

During the past two years, four reports have appeared, indicating that hypertension occurs in some women taking estrogengestagen combinations for control of conception or menstrual irregularities. Swaab (1) suggested that blood pressure could increase markedly during the use of oral contraceptives. Laragh (2) presented data on eleven patients with hypertension during contraceptive administration. In six of these patients, hypertension was first noted after starting medication. Six of the eight patients who stopped medication showed improvement or disappearance of the hypertension. In two cases, hypertension reappeared when medication was re-instituted. Woods (3) reported six patients with hypertension which was precipitated or aggravated by oral contraceptives.