HETEROGENEITY IN VASCULAR SMOOTH-MUSCLE RESPONSIVENESS TO ANGIOTENSIN-II - ROLE OF ENDOTHELIN

We compared the role of endothelium and of endothelin in mediating the vasoconstrictor responses to angiotensin II (Ang II) in three vascula r smooth muscle preparations-aorta, mesenteric artery, and tail artery -isolated from adult male Sprague-Dawley rats. The vasoconstrictor pot ency for Ang II in blood vessels with endothelium varied in the follow ing rank order: aorta>mesenteric artery>tail artery. Although the maxi mal tension responses to Ang II were similar for mesenteric and tail a rteries, it was significantly lower in aorta. Endothelium removal led to a leftward shift in the concentration-response curves to Ang II in the aorta but a rightward shift in the mesenteric artery. Strikingly, Ang II failed to evoke tension responses in tail artery in the absence of endothelium. The endothelin-A (ET(A))-selective antagonist BQ-123 blocked the responses to Ang II in a noncompetitive manner, with parti al and complete attenuation of responses in the endothelium-intact mes enteric and tail artery preparations, respectively. In contrast, BQ-12 3 did not affect the responses to Ang II in the aorta. BQ-123 also fai led to affect the responses to Ang II in endothelium-denuded mesenteri c artery rings. The Ang II type 1 (AT(1)) receptor-selective antagonis t losartan competitively blocked the responses to Ang II in the three tissues (pA(2), 8.3 to 8.7) when endothelium was present. These data s uggest that there are endothelium-dependent regional variations in vas cular tissue sensitivity to Ang II. The vasoconstrictor response to An g II in rat aorta involves activation of AT(1) receptors located on va scular smooth muscle cells, whereas the response in mesenteric artery involves activation of both vascular and endothelial AT(1) receptors. In contrast, the responses to Ang II in the tail artery may be mediate d by the indirect stimulation of vascular smooth muscle ET(A) receptor s subsequent to the activation of endothelial AT(1) receptors likely l inked to the release of endothelins.