(Stroke. 1995;26:682-687.)
© 1995 American Heart Association, Inc.
Articles |
Effect of Nitric Oxide Synthase Inhibition on the Cerebral Vascular Response to Hypercapnia in Primates
From the Department of Anesthesiology/Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md; and Cook County Hospital, Chicago, Ill (R.F.G.).
Correspondence to Robert W. McPherson, MD, Meyer 8-138, Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21287.
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
N
-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.
Key Words: cerebral blood flow • hypercapnia • nitric oxide • oxygen • monkeys
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