Increases in pulse pressure impair acetylcholine-induced vascular relaxation.
Effects of pulse pressure on acetylcholine-induced endothelium-dependent relaxation were investigated using a cascade bioassay model. Intact carotid arteries from rabbits were perfused at constant flow, and activity of endothelium-derived relaxing factor (EDRF) was assayed by measuring changes in isometric tension in a detector ring without endothelium. When pulse pressure of the donor artery was raised from approximately 2 to 10 mmHg, relaxation to acetylcholine (10(-7) M) was reduced from 31 +/- 3 (means +/- SE) to 20 +/- 2% (expressed as percent relaxation of phenylephrine-induced tone). Responses of the detector ring to nitroprusside were unchanged. Superoxide dismutase (SOD) and indomethacin each prevented impairment of relaxation to acetylcholine at high pulse pressure. When the donor artery was perfused at a higher mean pressure, elevation of pulse pressure also impaired relaxation to acetylcholine, and this impairment was prevented by SOD. These findings suggest that elevation of pulse pressure inhibits acetylcholine-induced, endothelium-dependent relaxation, and this inhibitory effect is mediated by generation of oxygen radicals.
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
S M
SM
Ryan
B J
BJ
Waack
B L
BL
Weno
D D
DD
Heistad
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D017536:Carotid Artery, Common / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011674:Pulse; D011817:Rabbits; D013481:Superoxides / Q000494:pharmacology
D013481:Superoxides; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D000109:Acetylcholine; D007213:Indomethacin