NITRIC-OXIDE REGULATES ENDOTHELIUM-DEPENDENT VASODILATOR RESPONSES INRABBIT HINDQUARTERS VASCULAR BED IN-VIVO

The objective of this study was to determine whether nitric oxide (NO) could function as a negative feedback modulator of endothelium-depend ent vasodilation in vivo. To this end, the influence of exogenous NO o n vasodilator responses in the rabbit hindquarters vascular bed was de termined. Previous in vitro studies have demonstrated that NO inhibits both neuronal NO synthase from rat cerebellum as well as NO synthase derived from bovine aortic endothelial cells. The present study was co nducted in the rabbit hindquarters vascular bed under conditions of co nstant blood flow so that changes in pressure directly reflected chang es in vascular resistance. Under these in vivo conditions, the NO dono r agent S-nitroso-N-acetylpenicillamine (SNAP) reversibly attenuated r esponses to the endothelium-dependent vasodilators, acetylcholine and bradykinin. In contrast, SNAP did not influence the endothelium-indepe ndent vasodilator response to SNAP itself or to 8-bromoguanosine 3',5' -cyclic monophosphate. These observations indicate clearly that NO int erferes with endothelium-dependent vasodilator action and support the view that endogenous NO may actually play a physiological role in regu lating vascular tone.