Hydrocortisone-Induced Hypertension in Men: The Role of Cardiac Output

Abstract

In previous studies we have shown that administration of 200 mg/day hydrocortisone (cortisol) to normal subjects raises blood pressure and cardiac output, with no change in total peripheral resistance or resting forearm vascular resistance. We have tested the hypothesis that this rise in cardiac output is essential for the rise in blood pressure (BP). Six normal volunteer men, aged 22 to 34 years, took part in two studies of 10 days, in random order, at least 4 weeks apart. Placebo (Study A) or 50 mg atenolol orally, 12 hourly (Study B), was given on days 1 to 10 and 50 mg cortisol orally, 6 hourly, on days 5 to 10. Blood pressure and cardiac output (Fick technique, alternative Doppler) were measured on days 4 and 10. In Study A (placebo and cortisol) systolic BP rose from 116 to 125 mm Hg (standard error of the difference, SED 1.5), P < .01, and in Study B (atenolol and cortisol) from 109 to 120 mm Hg (SED 1.5), P < .01. Cardiac output (indirect Fick) rose from 4.8 +/- 0.01 to 5.9 +/- 0.2 L/min, P < .01, in A, and was unchanged in Study B, 4.4 +/- 0.1 to 4.4 +/- 0.2 L/min. Cardiac output measured by Doppler method was similar in pattern, 5.1 +/- 0.2 to 6.7 +/- 0.2 L/min (P < .01) in A and 5.7 +/- 0.2 to 5.8 +/- 0.2 in B. Calculated peripheral resistance fell in Study A and increased in Study B.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential regional hemodynamic effects of corticotropin in conscious sheep.

“…27 Prevention of the increase in CO by /3-adrenergic receptor blockade had no effect on the degree of hypertension in DOC and DOCA-salt hypertensive dogs 25 ' 26 or in cortisol-induced hypertension in humans. 24 Similarly, in ACTH hypertension in sheep, /3-blockade prevented the increase in CO but not the rise in blood pressure, which increased because of an increase in total peripheral resistance. 12 Further evidence indicating that the increase in CO is not entirely a response to the increased plasma volume is the finding that the rise in CO during ACTH is prevented by ganglionic blockade 28 and clonidine, 29 suggesting that elevated cardiac sympathetic activity may play a role in the ACTH-induced increase in CO.…”

“…Further evidence that the increase in CO probably depends on both mineralocorticoid and glucocorticoid effects are the findings in humans that CO increases during the early phase of primary aldosteronism 23 and during infusion of cortisol. 24 Furthermore, CO is elevated in canine deoxycorticosterone (DOC) 25 and deoxycorticosterone acetate (DOCA)-salt hypertension 26 and during DOCA-salt hypertension in rats. 27 Prevention of the increase in CO by /3-adrenergic receptor blockade had no effect on the degree of hypertension in DOC and DOCA-salt hypertensive dogs 25 ' 26 or in cortisol-induced hypertension in humans.…”

Glucocorticoid-Mediated Hypertension

“…Previous studies have shown that glucocorticoids increase cardiac output, 14 but this increase was not believed to play a major role in mediating the increase in BP in humans. This will need to be reexamined in future studies using these Sm-GC knockout mice and mice with selective deletion of the cardiac glucocorticoid receptor.…”

Cushing, Cortisol, and Cardiovascular Disease

“…Cardiac output is increased, but this is not essential for the rise in blood pressure, 42 and sympathetic activity is decreased. [43][44][45] Cortisol has a variety of effects on kidneys, heart, brain, blood vessels, and body fluid volumes, but it is not clear which of these are causal rather than epiphenomena or amplifiers or modulators of the rise in blood pressure.…”