EFFECTS OF PHENTOLAMINE OR YOHIMBINE ON NALOXONES ACTIONS DURING ENDOTOXIN-SHOCK IN RATS

Endogenous opioids are known to mediate some of the cardiovascular seq uelae of sepsis. Inhibition of adrenergic action has been implicated a s a physiological path by which endogenous opioids cause deleterious c hanges in cardiovascular function during endotoxin shock, but where an d to what extent this accounts for changes in regional vascular resist ance remains unclear. In this study, we addressed this question by exa mining the role of alpha-adrenergic actions in cardiovascular performa nce and the regional perfusion changes caused by naloxone during endot oxin shock. Rats had catheters inserted into the tail artery, left car diac ventricle, and jugular vein. Twenty-four hours later, rats receiv ed saline or endotoxin (2 mg/kg) challenge intravenously over 30 min, followed at 40 min by intravenous naloxone (or saline) treatment (4 mg /kg + 2 mg/kg . h) in the presence or absence of phentolamine (100 mu g/kg + 600 mu g/kg . h) or yohimbine (40 mu g/kg + 4 mu g/kg . h). Rad iolabeled microspheres were used to determine cardiac outputs and bloo d flows at 0, 30, 60, and 120 min after beginning endotoxin infusion. Naloxone attenuated the endotoxin-induced decline in mean arterial pre ssure (MAP) and cardiac output (GO), but had no effect on increased sy stemic vascular resistance (SVR). Phentolamine blocked naloxone's abil ity to increase MAP and CO, but permitted an increase in SVR by naloxo ne. In the presence of yohimbine, naloxone still increased MAP, but no t CO nor SVR. Regional vascular responses varied, with naloxone demons trating a vasoconstrictive effect despite alpha-adrenergic receptor bl ockade in some beds, and no effect in others. The response of individu al organs in the hepatosplanchnic circulation was heterogenous as well . These data suggest that some effects of endogenous opioids during en dotoxin shock are mediated via inhibition of alpha-adrenergic effects, but that some cardiovascular effects of endogenous opioids are indepe ndent of adrenergic control during endotoxin shock.