Endothelin and angiotensin il-induced contraction of the rat tail artery - pharmacology of the signalling pathways
Angiotensin II (All) mediates vasoconstriction via the activation of All receptors (predominately ATI A subtype) on vascular smooth muscle cells. However, a role for All-mediated endothelin (ET-1) release from endothelial cells has been suggested from studies with the rat tail artery preparation. We have determined the contractile effects of All and ET-1 in endotheliumintact and denuded ring preparations from the rat tail artery as well as freshly dispersed single smooth muscle cells from the same tissue. Our data indicate that: (i) the contractile effects of All and ET-1 are endothelium-independent and are antagonized respectively by losartan and BQ-123, the AT, and ETA selective antagonists; (ii) The All-mediated response is dependent on intracellular Ca2+ release-whereas that of ET-1 was primarily dependent on extracellular Ca2+ entry, and can thus be pharmacologically distinguished by the use of caffeine and nifedipine respectively. These data indicate that All and ET-1 utilize distinct signalling pathways in the rat tail artery, and that the response to All does not involve ET-1 release from the endothe-lium.