CARDIOVASCULAR REGULATION BY ENDOGENOUS NITRIC-OXIDE IS ESSENTIAL FORSURVIVAL AFTER ACUTE HEMORRHAGE

Our previous studies have indicated that endogenous nitric oxide serve s as a physiologically important inhibitor of vascular tone during acu te haemorrhage. This vasodilator action attenuates the concomitant ref lex adrenergic constriction and thereby prevents critical reduction of tissue blood flow. The present study aimed to evaluate the overall im portance of this nitric oxide regulation for survival after acute haem orrhage. This was done by comparative observations of survival time an d circulatory, metabolic and histopathological changes after an acute standardized lethal blood loss (45%) in cats exposed to nitric oxide s ynthase (NOS) inhibition and in matched control animals with intact ni tric oxide regulation. NOS inhibition was instituted by intravenously administered N-omega-nitro-L-arginine methyl ester. The survival time averaged 2 h 49 min in the NOS-blocked animals and 10 h 24 min in the control animals (P < 0.001). NOS inhibition thus reduced the posthaemo rrhagic survival time to < 30% of that in the control cats. Haemorrhag e in the NOS-blocked animals led to rapidly developing arterial hypote nsion. increased anaerobic metabolism. metabolic lactacidosis. hyperka laemia, and morphological tissue damage especially in heart and liver, in spite of maintained arterial normoxia. which signifies tissue hypo xia caused by seriously impaired nutritional blood supply. At the time of death of the NOS-blocked cats, the control animals still exhibited a virtually normal circulatory/metabolic state. A much later, and mor e slowly developing circulatory/metabolic deterioration was observed i n the control animals. These differences between the two groups of ani mals indicate that nitric oxide release. by its vasodilator action, to a significant extent helps to maintain an adequate nutritional blood supply to the tissues in acute haemorrhage.