CORRECTION OF HYPOVOLEMIC HYPOTENSION BY CENTRALLY ADMINISTERED NALOXONE IN CONSCIOUS RABBITS

Our goal was to test directly whether the vasoconstrictor action of na loxone during hypovolemic hypotension is centrally mediated. In eight chronically instrumented rabbits, progressive central hypovolemia and fall in cardiac output (GO) were produced by gradually inflating a cuf f on the thoracic vena cava. Central hypovolemia was then sustained fo r 8 min by holding CO constant. In the main experiment (n = 4), each r abbit was studied eight times over 4 experimental days. Saline or nalo xone treatment commenced 10 min before progressive hypovolemia (early treatment) or 2 min after the onset of sustained hypovolemia (late tre atment), given by intravenous infusion or into the fourth ventricle (V -4) With saline treatment, there was spontaneous recovery of systemic vasoconstriction and arterial pressure during sustained hypovolemia. L ate treatment with naloxone (4 mg/kg iv; 4-37 mu g/kg V-4) accelerated and exaggerated these changes. Thus, under conditions of constant CO and central blood volume, the vasodilatation of the decompensatory pha se of acute hypovolemia is not sustained, and intravenous naloxone's v asoconstrictor action is via a brain stem mechanism.