STUDY ON THE MECHANISMS OF GLUCOCORTICOID-INDUCED HYPERTENSION - GLUCOCORTICOIDS INCREASE TRANSMEMBRANE CA2-MUSCLE IN-VIVO( INFLUX IN VASCULAR SMOOTH)

Blood pressure (BP) and ex vivo influx rate of Ca2+ in excised aortae were measured in rabbits implanted with silastic rubber strips impregn ated with glucocorticoids (GC) [dexamethasone (DEX) or cortisol (F-K)] , or carbenoxolone (CX) [inhibitor of 11 beta-hydroxysteroid dehydroge nase (11-HSD), in a large (lg) or a small (sm) (10 limes smaller) conc entration], or F-K plus CX (sm), or DEX plus RU 38486 (a specific CC-r eceptor blocker). After 4-6 weeks rabbits implanted with DEX, CX (Ig), and F-K + CX (sm) developed hypertension. Those implanted with F-K al one (yielding physiological serum concentration of F-K), CX (sm), and DEX + RU 38486 did not develop hypertension. Rates of unidirectional i nflux of Ca2+ measured in rings of excised aortae were in all hyperten sive rabbits more than twice those in the control rabbits (implanted w ith silastic strips not containing any steroids). In all normotensive rabbits, Ca2+ influx rates remained normal. We conclude that, in analo gy with the in vitro findings in cultured vascular smooth muscle (VSM) cells treated with GC, also in vivo the elevation of tissue levels of GC causes an increase in the influx rate of Ca2+ in VSM. We propose t hat this may be the main pathogenic mechanism of GC-induced hypertensi on.