Effects of antiglucocorticoids on glucocorticoid hypertension in the rat.
The early phase of hypertension induced in rats by a glucocorticoid agonist RU 26988 was studied. Systolic blood pressure increased by 35 mm Hg. Water and sodium urinary excretion increased transiently, and plasma volume decreased. Total and ouabain-sensitive sodium efflux, as well as rubidium efflux, were enhanced by glucocorticoid administration. Low salt intake did not prevent hypertension. Pretreatment with RU 38486, a steroid with antiglucocorticoid properties, largely prevented the rise in blood pressure (+10 mm Hg) and suppressed transient natriuresis and the decrease in plasma volume. Changes in total and ouabain-sensitive sodium efflux were completely prevented, whereas changes in rubidium efflux were only partly reversed. Similarly, administration of progesterone, a steroid with antiglucocorticoid effects, prevented glucocorticoid hypertension (+11 mm Hg) and vascular ionic changes. In contrast administration of RU 28318, an antimineralocorticoid agent, was without effect on glucocorticoid hypertension (+38 mm Hg). Progesterone or RU 38486 administered after glucocorticoid also decreased blood pressure. Present data indicate that glucocorticoid hypertension may be prevented or reversed in its early phase by steroid drugs with antiglucocorticoid properties. These drugs also appeared to prevent the sodium and rubidium flux abnormalities induced by glucocorticoid. We suggest that activation of the vascular glucocorticoid receptors may be involved in the pathophysiology of glucocorticoid hypertension.
D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D004963:Estrenes / Q000494:pharmacology; D005938:Glucocorticoids / Q000037:antagonists & inhibitors*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology* / Q000652:urine; D015735:Mifepristone; D009318:Natriuresis / Q000187:drug effects; D011374:Progesterone / Q000097:blood / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology
D000732:Androstanols; D004963:Estrenes; D005938:Glucocorticoids; D013148:Spironolactone; D015735:Mifepristone; D011374:Progesterone; C038341:RU 26988; C041006:RU 28318; D012964:Sodium