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 Pco(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 Pco(2) of approximate to 70 mm Hg (high-CO2 group, n=5) and Pco(2) of approximate to 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 N omega-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 reg, 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+/-0.1 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 odde contributes to basal vascular tone but is not a major contributor to the mechanism of hypercapnia-induced cerebral vasodilation, except in cortex, in primates.