Neuronal nitric oxide synthase mediates halothane-induced cerebral microvascular dilation

Background: The causes of volatile anesthetic-induced cerebral vasodilation include direct effects on smooth muscle and indirect effects via changes i n metabolic rate and release of mediators from vascular endothelium and bra in parenchyma. The role of nitric oxide and the relative importance of neur onal and endothelial nitric oxide synthase (nNOS and eNOS, respectively) ar e unclear. Methods: Rat brain slices were superfused with oxygenated artificial cerebr ospinal fluid. Hippocampal arteriolar diameters were measured using compute rized videomicrometry. Vessels were preconstricted with prostaglandin F-2 a lpha (PGF(2 alpha); halothane group) or pretreated with 7-nitroindazole sod ium (7-NINA, specific nNOS inhibitor, 7-NINA + halothane group) or N-nitro- L-arginine methylester CL-NAME; nonselective NOS inhibitor, L-NAME + haloth ane group) and subsequently given PGF(2+) to achieve the same total precons triction as in the halothane group. Increasing concentrations of halothane were administered and vasodilation was calculated as a percentage of precon striction. Results: Halothane caused significant, dose-dependent dilation of hippocamp al microvessels (halothane group). Inhibition of nNOS by 7-NINA or nNOS + e NOS by L-NAME similarly attenuated halothane-induced dilation at 0.6, 1.6, and 2.6% halothane. The dilation (mean +/- SEM) at 1.6% halothane was 104 /- 10%, 65 +/- 6%, and 51 +/- 9% in the halothane, 7-NINA + halothane and L -NAME + halothane groups, respectively. The specificity of 7-NINA was confi rmed by showing that acetylcholine-induced dilation was not inhibited by 7- NINA but was converted to constriction by L-NAME. Conclusions: At clinically relevant concentrations, halothane potently dila tes intracerebral arterioles, This dilation is mediated, in part, by neuron ally derived nitric oxide. Endothelial NOS does not play a major role in ha lothane-induced dilation of hippocampal microvessels.