Study on the mechanisms of glucocorticoid-induced hypertension: glucocorticoids increase transmembrane Ca2+ influx in vascular smooth muscle in vivo.
Blood pressure (BP) and ex vivo influx rate of Ca2+ in excised aortae were measured in rabbits implanted with silastic rubber strips impregnated with glucocorticoids (GC) [dexamethasone (DEX) or cortisol (FK)], or carbenoxolone (CX) [inhibitor of 11 beta-hydroxysteroid dehydrogenase (11-HSD), in a large (lg) or a small (sm) (10 times smaller) concentration], or FK plus CX (sm), or DEX plus RU 38486 (a specific GC-receptor blocker). After 4-6 weeks rabbits implanted with DEX, CX (lg), and FK+CK (sm) developed hypertension. Those implanted with FK alone (yielding physiological serum concentration of FK), CX (sm), and DEX+RU 38486 did not develop hypertension. Rates of unidirectional influx of Ca2+ measured in rings of excised aortae were in all hypertensive rabbits more than twice those in the control rabbits (implanted with silastic strips not containing any steroids). In all normotensive rabbits, Ca2+ influx rates remained normal. We conclude that, in analogy 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 that this may be the main pathogenic mechanism of GC-induced hypertension.
Kornel
L
L
Department of Medicine (Section of Endocrinology), Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
Prancan
A V
AV
Kanamarlapudi
N
N
Hynes
J
J
Kuzianik
E
E
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D005938:Glucocorticoids / Q000633:toxicity*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits
D005938:Glucocorticoids; D002118:Calcium