Brain cyclic-AMP and possible mechanisms of cerebrovascular dilation by anesthetics in rats

Barbiturates decrease both cerebral metabolic rate (CMR) and cerebral blood flow (CBF) and thereby preserve CBF and CMR coupling. However, many inhalation agents and ketamine uncouple CBF and CMR by virtue of inducing disproportionate increases in CBF. Adenosine 3',5'-monophosphate (cyclic-AMP) reportedly mediates uterine and aortic smooth muscle relaxation by halothane and may also mediate CBF-CMR uncoupling by anesthetics. Therefore, the authors studied the effect of various doses of halothane and ether on brain cyclic-AMP and compared them with the effects of ketamine and pentobarbital anesthesia. Both halothane 1.5 and 2.0 per cent and ether, 2.5 to 7.5 per cent (inspired concentrations) increased whole brain cyclic-AMP above unanesthetized levels (1,046 +/- 75 pmol/g wet brain) in a dose-related manner. Ketamine, 150 mg/kg, ip, increased brain cyclic-AMP twofold, whereas an apparent increase by 60 mg/kg pentobarbital, ip, was not significant. These results show a dose-related effect of ether and halothane on brain cyclic-AMP levels and suggest a causal relationship to their cerebrovasodilatory effects.