L-arginine and nitroglycerin restore hypercapnia-induced cerebral vasodilation in rabbits after its attenuation by ketamine

Although it has been reported that ketamine attenuates hypercapnia-induced cerebral vasodilation, the mechanism remains unknown. Because nitric oxide is involved in cerebral CO2 reactivity, we studied the effects of L-arginine and nitroglycerin on ketamine-mediated attenuation of vascular responses to hypercapnia. Under pentobarbital anesthesia, 16 rabbits underwent closed cranial window preparation. Hypercapnic challenges were repeated after IV saline, ketamine (10 mg/kg, followed by 20 mg x kg(-1) x h(-1)), or ketamine plus either L-arginine (150 mg/kg, followed by 100 mg x kg(-1) x h(-1); n = 8) or nitroglycerin (5 microg x kg(-1) x min(-1) infusion; n = 8). Ketamine reduced hypercapnia-induced cerebral vasodilation (1.27%/mm Hg +/- 0.45%/mm Hg [saline] versus 0.82%/mm Hg +/- 0.53%/mm Hg [ketamine]: P < 0.05), but L-arginine restored reactivity (1.28%/mm Hg +/- 0.73%/mm Hg: P < 0.05 versus ketamine), as did nitroglycerin (1.14%/mm Hg +/- 0.73%/mm Hg [saline] versus 0.56%/mm Hg +/- 0.63%/mm Hg [ketamine]: P < 0.05, and 1.15%/mm Hg +/- 0.74%/mm Hg [ketamine plus nitroglycerin]: P < 0.05 versus ketamine). This indicates that ketamine attenuates cerebral CO2 reactivity, at least in part, via suppression of nitric oxide-cyclic guanosine monophosphate mechanisms in the cerebral vasculature. IMPLICATIONS: The attenuation of cerebral vasodilation to hypercapnia seen under ketamine anesthesia is reversed by L-arginine or nitroglycerin infusion.