Calcium antagonists block angiotensin II-mediated vasoconstriction in humans: comparison with their effect on phenylephrine-induced vasoconstriction.
Calcium antagonists are known to decrease peripheral vascular resistance in vivo in humans. The mechanism of this vascular relaxation has not been clearly elucidated. Vascular tone is maintained by several endogenous neurohumoral systems including sympathetic nervous system activity and angiotensin II. We compared and contrasted the capacity of calcium antagonist drugs to prevent angiotensin II and phenylephrine-induced alpha-1 adrenergic vasoconstriction using brachial artery infusion and measurement of forearm blood flow by strain gauge plethysmography. In a dose-dependent manner, calcium antagonists blocked angiotensin II-induced vasoconstriction. The rank order of this blockade was nifedipine greater than verapamil greater than diltiazem. Nifedipine and verapamil, but not diltiazem blocked alpha-1 adrenergic (phenylephrine-induced) vasoconstriction. At 7.64 and 19.1 micrograms/min infusion rates for nifedipine and verapamil, respectively, they abolished the angiotensin II effect; however, the phenylephrine effect was incompletely blocked. Calcium antagonist-induced vascular relaxation in vivo in humans is in part explained by their capacity to block angiotensin II-mediated vasoconstriction. In addition, two calcium antagonists (nifedipine and verapamil) may inhibit alpha-1 adrenergic vasoconstriction.
Andrawis
N S
NS
Program in Clinical Pharmacology, Brown University, Providence, Rhode Island.
Craft
N
N
Abernethy
D R
DR
D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D004110:Diltiazem / Q000494:pharmacology*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D010656:Phenylephrine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology*
D000804:Angiotensin II; D010656:Phenylephrine; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine