Endothelium-dependent response of the rabbit aorta to femtomolar concentrations of angiotensin II.
Thirty-five percent of endothelium-intact rabbit aortic rings tested contracted biphasically to angiotensin II (AII). The threshold concentration in these rings varied, ranging from 10(-16) to 10(-12) M. The remaining 65% contracted monophasically with a range of threshold concentrations of 10(-11)-10(-8) M. All endothelium-denuded rings tested contracted monophasically with a threshold concentration of 10(-10)-10(-8) M. The contractions of both types of rings were inhibited by 1-sar-8-ala-angiotensin II, but not phentolamine or indomethacin, indicating that the contractions were not mediated by secondary agonists such as noradrenaline or arachidonic acid metabolites. Bioassay studies revealed that 10(-16) M AII released an endothelial factor that modulated the action of AII, converting the monophasic response of an endothelium-denuded ring to a biphasic response to AII (10(-16)-10(-7) M). The results demonstrate for the first time the endothelium-dependent response of an artery to femtomolar concentrations of AII and support the existence of arterial angiotensin receptors capable of being saturated by circulating levels of the hormone.
Kuttan
S C
SC
Department of Pharmacology, Faculty of Medicine, National University of Singapore.
Sim
M K
MK
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008832:Microchemistry; D009119:Muscle Contraction / Q000187:drug effects; D009994:Osmolar Concentration; D010646:Phentolamine / Q000494:pharmacology; D011817:Rabbits; D012504:Saralasin / Q000494:pharmacology
D000804:Angiotensin II; D012504:Saralasin; D007213:Indomethacin; D010646:Phentolamine