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.