Effect of different calcium channel blockers on angiotensin II- and vasopressin-induced prostacyclin biosynthesis in vascular smooth muscle cells.
To gain insight with regard to the mode of action of calcium antagonists on the vasculature, we examined the effects of nifedipine, isradipine, felodipine, verapamil, gallopamil, and amlodipine on vasoconstrictor-induced prostacyclin synthesis in vitro. Cultured rat aortic smooth muscle cells were seeded after two to four passages in multiwell plates. After washing of the culture medium and a preincubation period, the cells were exposed for 1 h to either angiotensin II (Ang II) or arginine-vasopressin (AVP) at increasing concentrations between 10(-10)-10(-6) M with or without each calcium antagonist tested at 10(-6) M. At the end of the incubation period, the medium was aspirated, centrifuged, and assayed for its content of protein and of 6-keto-PGF1 alpha by radioimmunoassay. Ang II induced a 15-fold increase and AVP induced a fivefold increase of 6-keto-PGF1 alpha at 10(-6) M. None of the various calcium channel blockers tested showed a significant effect on this agonist-stimulated production of 6-keto-PGF1 alpha. Consequently, calcium-channel blockers with different chemical structure, although known to inhibit agonist-induced vasoconstriction, appear to preserve vasoconstrictor-induced production of prostacyclin, a potent vasodilator and an inhibitor of platelet aggregation.
Department of Medicine, University Hospital, Geneva, Switzerland.
M B
MB
Vallotton
C
C
Gerber-Wicht
W
W
Dolci
R W
RW
Rivest
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D004347:Drug Interactions; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D000804:Angiotensin II; D001127:Arginine Vasopressin; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol