Characterization of vasoconstrictor responses in small bovine adrenal cortical arteries in vitro

Abstract

The adrenal gland is highly vascularized with tightly regulated blood flow that is closely correlated with steroidogenesis. Mechanisms involved in the regulation of adrenal blood flow and vascular tone are largely unknown. The present study characterizes the contractile responses of isolated small cortical arteries from bovine adrenal glands. In endothelium-intact arteries, K+, the thromboxane mimetic U46619, 5-hydroxytryptamine (5-HT), and endothelin-1 (ET-1) induced concentration-dependent contractions, whereas phenylephrine, norepinephrine, and ACTH were without effect. The EC 50s for K+, U46619, 5-HT, and ET-1 were 45 ± 3 mM, 150 ± 24 nM, 370 ± 38 nM, and 2.8 ± 0.8 nM, respectively. Contractions induced by U46619, 5-HT, and ET-1 were blocked by the thromboxane receptor antagonist SQ 29,548, the 5-HT2A receptor antagonist ketanserin, and the ETA receptor antagonist BQ 123, respectively. Removal of the endothelium caused a marked leftward shift of concentration responses to high K+, U46619, 5-HT, and ET-1, and revealed contractile responses to phenylephrine and norepinephrine. In U46619-preconstricted arteries, BQ 123 converted ET-1-induced contractions to relaxations (maximal relaxation of 57 ± 8%), which were subsequently blocked by the ETB receptor antagonist BQ 788. The ET B-mediated relaxations were endothelium dependent and inhibited by the nitric oxide synthase inhibitor N-nitro-L-arginine, the cytochrome P450 inhibitor SKF 525A, and high extracellular K+, but not by the cyclooxygenase inhibitor indomethacin. These results demonstrate that small adrenal cortical arteries are highly responsive to various vasoconstrictor agents. The forceful contractile responses of these arterioles are consistent with their potential role in the regulation of adrenal blood flow.