SUMMARY Acute subcutaneous (s.c.) administration of aldosterone increases ex vivo "Na efflux from rat tail artery smooth muscle, which appears to be due to a specific action on mineralocorticoid receptors. Indeed, this effect is blocked by the antimineralocorticoid compounds RU 28318 [17/3-hydroxy-3-oxo,7 a-propyl(17 a)-pregn 4-ene, 21 potassium carboxylate] and spironolactone. The specific glucocorticoid receptor agonist RU 26988 [ll/3,17/3-dihydroxy-17-(l-propynyl) androesta-1,4,6 trien-3-one] does not modify M Na efflux. We show here that aldosterone has, at physiological concentrations, a mineralocorticoid specific stimulating effect on passive and sodium pump dependent transmembrane movements of sodium from the rat tail artery smooth muscle. Aldosterone exerts two types of action on sodium transport: 1) a delayed stimulation of ouabain-dependent M Na efflux and ouabaln-independent

SUMMARY 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. (Hypertension 7: 292-299, 1985 We therefore initiated a study of the in vivo effects of RU 26988 in the rat. RU 26988 is a specific glucocorticoid receptor agonist that exhibits high affinity for glucocorticoid receptor sites and does not compete with aldosterone for the mineralocorticoid receptor."12 We attempted to antagonize glucocorticoidinduced hypertension by administration of an antimineralocorticoid (RU 28318) and steroid derivatives known to bind competitively at the glucocorticoid receptor-progesterone and RU 38486. The latter steroid has mainly antiprogesterone properties; in vitro studies have also shown antiglucocorticoid activity. 13-I4 Lastly, we investigated the ionic changes induced by glucocorticoid and antiglucocorticoids on the rat tail artery after in vivo administration of the steroid drugs.

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