Interaction of vasopressin and angiotensin II in stimulation of prostacyclin synthesis in vascular smooth muscle cells.
The effect of angiotensin II (ANG II) and arginine vasopressin (AVP) on prostacyclin production by vascular smooth muscle cells (VSMC) has been examined. Cultured rat aortic VSMC were studied during either static incubation in multiwell plates or during dynamic incubation in superfusion columns. Prostacyclin synthesis was assessed by radioimmunoassaying one of its stable metabolites, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). Both ANG II and AVP stimulated the biosynthesis of prostacyclin in a concentration-dependent manner (10(-10) to 10(-5) M). ANG II (ED50 = 3 nM) displayed a higher potency than AVP (ED50 = 10 nM). ANG II was 4.4 times more potent than AVP at 10(-8) M. The effect of both peptides was inhibited selectively by antagonists. In the case of AVP (10(-8) M), a pure V1 antagonist (dEt2AVP) and the V2 agonist dDAVP, both at 10(-6) M, completely blocked the production of prostacyclin induced by AVP, whereas a mixed V1-V2 antagonist [d(CH2)5-D-Leu-VAVP] at 10(-6) M displaced the concentration-response curve by approximately two orders of magnitude to the right. Superfusion with a calcium-free medium containing ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid inhibited 89 +/- 3% of the ANG II- and 70 +/- 8% of the AVP-induced prostacyclin production, whereas nifedipine (10(-6) M) had no effect. A potentiating effect was observed when the stimulation with either ANG II or AVP was repeated two or three times. An even more marked potentiation resulted when the stimulation by ANG II (10(-8) M) followed stimulation by AVP (10(-8) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Vallotton
M B
MB
Department of Medicine, University Hospital, Geneva, Switzerland.
Gerber-Wicht
C
C
Dolci
W
W
Wüthrich
R P
RP
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D004347:Drug Interactions; D004357:Drug Synergism; D011464:Epoprostenol / Q000096:biosynthesis*; D005110:Extracellular Space / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D013268:Stimulation, Chemical
D002121:Calcium Channel Blockers; D000804:Angiotensin II; D001127:Arginine Vasopressin; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D002118:Calcium