Effect of Nitric Oxide Synthase Inhibition on the Cerebral Vascular Response to Hypercapnia in Primates

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Abstract
Background and Purpose The role of nitric oxide in cerebrovascular response to changes in P co 2 is unclear. In the present study, we assessed responses at two levels of hypercapnia in a primate model before and after blockade of nitric oxide synthesis. Methods We compared the effects of two levels of hypercapnia, defined as P co 2 of ≈70 mm Hg (high-CO 2 group, n=5) and P co 2 of ≈50 mm Hg (moderate-CO 2 group, n=6), on increases in regional cerebral blood flow (microspheres) before and after inhibition of nitric oxide synthase with N ω -nitro- l -arginine methyl ester (L-NAME; 60 mg · kg −1 ) in isoflurane-anesthetized cynomolgus monkeys (1.0% end-tidal concentration). Results Before L-NAME administration, hypercapnia increased flow in all regions (eg, forebrain: high-CO 2 group, 69±10 to 166±15 mL · min −1 · 100 g −1 ; moderate-CO 2 group, 49±7 to 93±15 mL · min −1 · 100 g −1 ) and decreased cerebral vascular resistance (high-CO 2 , 1.1±0.1 to 0.4±0.1 mm Hg · mL −1 · min · 100 g; moderate-CO 2 , 1.4±0.1 to 0.7±0.1 mm Hg · mL −1 · min · 100 g). During normocapnia, L-NAME decreased cerebral blood flow (high-CO 2 , 37±9%; moderate-CO 2 , 40±6%) and increased cerebral vascular resistance (high-CO 2 , 93±33%; moderate-CO 2 , 88±20%). After L-NAME, hypercapnia still increased blood flow in all regions (eg, forebrain: high-CO 2 , 56±7 to 128±3 mL · min −1 · 100 g −1 ; moderate-CO 2 , 36±5 to 57±8 mL · min −1 · 100 g −1 ) and decreased vascular resistance (high-CO 2 , 1.5±0.1 to 0.6±0.1 mm Hg · mL −1 · min · 100 g; moderate-CO 2 , 2.0±0.3 to 1.2±0.1 mm Hg · mL −1 · min · 100 g). In both groups L-NAME attenuated hypercapnia hyperemia by approximately 30% in cortex but not in other regions. Conclusions Nitric oxide contributes to basal vascular tone but is not a major contributor to the mechanism of hypercapnia-induced cerebral vasodilation, except in cortex, in primates.