INFLUENCE OF NITRIC-OXIDE ON THE HEMODYNAMIC-RESPONSE TO HEMORRHAGE IN CONSCIOUS RABBITS

The investigated the role of nitric oxide, an endothelium-derived rela xing factor, in the hemodynamic response to acute hemorrhage in consci ous rabbits. Chronically instrumented rabbits were treated with the ni tric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) or vehicle and hemorrhaged until mean arterial pressure fell below 40 mmHg. Control animals were treated with L-NAME or vehicle but not sub jected to hemorrhage. L-NAME increased mean arterial pressure and decr eased heart rate in control animals. Hindquarters and mesenteric blood flow velocity and conductance were reduced by L-NAME. Nitric oxide sy nthase inhibition also produced significant changes in the hemodynamic response to hypotensive hemorrhage. Mean arterial pressure was higher and regional vascular conductances were lower throughout hemorrhage a nd during recovery. L-NAME treatment significantly (but in some cases, subtly) altered the characteristic pattern of changes in vascular con ductance associated with acute hypotensive hemorrhage and recovery. Si milar experiments with other arginine analogues or phenylephrine infus ion showed that L-NAME's effects during hemorrhage were due to nitric oxide synthase inhibition. We conclude that nitric oxide plays a role in the hemodynamic response to acute hemorrhage in the rabbit and is e ssential for the full expression of the vasodilation associated with h ypotensive hemorrhage.