Neuronal Nitric Oxide Synthase Mediates Halothane-induced Cerebral Microvascular Dilation

Michael Staunton, Cathy Drexler, Phillip G. Schmid, Heather S. Havlik, Antal G. Hudetz, Neil E. Farber
2000 Anesthesiology  
The causes of volatile anesthetic-induced cerebral vasodilation include direct effects on smooth muscle and indirect effects via changes in metabolic rate and release of mediators from vascular endothelium and brain parenchyma. The role of nitric oxide and the relative importance of neuronal and endothelial nitric oxide synthase (nNOS and eNOS, respectively) are unclear. Methods: Rat brain slices were superfused with oxygenated artificial cerebrospinal fluid. Hippocampal arteriolar diameters
more » ... riolar diameters were measured using computerized videomicrometry. Vessels were preconstricted with prostaglandin F 2␣ (PGF 2␣ ; halothane group) or pretreated with 7-nitroindazole sodium (7-NINA, specific nNOS inhibitor, 7-NINA ؉ halothane group) or N-nitro-Larginine methylester (L-NAME; nonselective NOS inhibitor, L-NAME ؉ halothane group) and subsequently given PGF 2␣ to achieve the same total preconstriction as in the halothane group. Increasing concentrations of halothane were adminis-tered and vasodilation was calculated as a percentage of preconstriction. Results: Halothane caused significant, dose-dependent dilation of hippocampal microvessels (halothane group). Inhibition of nNOS by 7-NINA or nNOS ؉ eNOS 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 confirmed by showing that acetylcholineinduced dilation was not inhibited by 7-NINA but was converted to constriction by L-NAME. Conclusions: At clinically relevant concentrations, halothane potently dilates intracerebral arterioles. This dilation is mediated, in part, by neuronally derived nitric oxide. Endothelial NOS does not play a major role in halothane-induced dilation of hippocampal microvessels. (
doi:10.1097/00000542-200001000-00023 pmid:10638908 fatcat:gshv4iaef5bhtjyelyzgd3dkxu