Effect of nitric oxide synthase inhibition on the cerebral vascular response to hypercapnia in primates

Background and Purpose: The role of nitric oxide in cerebrovascular response to changes in PCO₂ 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 PCO₂ of ≃70 mm Hg (high-CO₂ group, n=5) and PCO₂ of ≃50 mm Hg (moderate-CO₂ group, n=6), on increases in regional cerebral blood flow (microspheres) before and after inhibition of nitric oxide synthase with Nω-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-CO₂ group, 69±10 to 166±15 mL · min^-1- 100 g^-1; moderate-CO₂ group, 49±7 to 93±15 mL · min^-1 · 100 g^-1) and decreased cerebral vascular resistance (high-CO₂, 1.1±0.1 to 0.4±0.1 mm Hg · mL^-1 · min · 100 g; moderate-CO₂, 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-CO₂, 37±9%; moderate-CO₂, 40±6%) and increased cerebral vascular resistance (high-CO₂, 93±33%; moderate-CO₂, 88±20%). After L-NAME, hypercapnia still increased blood flow in all regions (eg, forebrain: high-CO₂, 56±7 to 128±3 mL · min^-1 · 100 g^-1; moderate- CO₂, 36±5 to 57±8 mL · min^-1 · 100 g^-1) and decreased vascular resistance (high-CO₂, 1.5±01 to 0.6±0.1 mm Hg · mL^-1 · min · 100 g; moderate-CO₂, 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.