Effect of nitric oxide synthase inhibition on the cerebral vascular response to hypercapnia in primates.
OBJECTIVE
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 approximately 70 mm Hg (high-CO2 group, n = 5) and PCO2 of approximately 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 (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 +/- 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 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.
McPherson
R W
RW
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Md 21287, USA.
Kirsch
J R
JR
Ghaly
R F
RF
Traystman
R J
RJ
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D000882:Haplorhini; D006935:Hypercapnia / Q000201:enzymology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D010100:Oxygen / Q000097:blood
D002245:Carbon Dioxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester