Neuronal nitric oxide synthase mediates halothane-induced cerebral microvascular dilation

Area of Science:

• Neuroscience
• Anesthesiology
• Vascular Biology

Background:

• Volatile anesthetics cause cerebral vasodilation through various mechanisms.
• The precise roles of nitric oxide (NO) and its synthases (neuronal NOS and endothelial NOS) in this process remain unclear.

Purpose of the Study:

• To investigate the contribution of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) to halothane-induced cerebral vasodilation.

Main Methods:

• Rat brain slices were used with computerized videomicrometry to measure hippocampal arteriolar diameters.
• Vessels were preconstricted and then exposed to increasing halothane concentrations.
• Specific (7-nitroindazole sodium) and non-selective (N-nitro-L-arginine methylester) NOS inhibitors were employed to assess NO pathway involvement.

Main Results:

• Halothane induced a dose-dependent dilation of hippocampal microvessels.
• Inhibition of nNOS (using 7-nitroindazole sodium) or both nNOS and eNOS (using N-nitro-L-arginine methylester) significantly attenuated halothane-induced vasodilation.
• Acetylcholine-induced dilation was unaffected by 7-nitroindazole sodium, confirming its specificity, but was reversed to constriction by N-nitro-L-arginine methylester.

Conclusions:

• Halothane causes potent dilation of intracerebral arterioles at clinical concentrations.
• Neuronally derived nitric oxide is a significant mediator of halothane-induced cerebral vasodilation.
• Endothelial NOS plays a minimal role in the dilation of hippocampal microvessels by halothane.