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

Abstract

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 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.

• Authors: R W McPherson, J R Kirsch, R F Ghaly, R J Traystman
• Journal: Stroke (Stroke) Vol. 26 Issue 4 Pg. 682-7 (Apr 1995) ISSN: 0039-2499 [Print] United States
• PMID: 7535954 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Carbon Dioxide
• Arginine
• Nitric Oxide Synthase
• Amino Acid Oxidoreductases
• Oxygen
• NG-Nitroarginine Methyl Ester

Topics

• Amino Acid Oxidoreductases (antagonists & inhibitors)
• Animals
• Arginine (analogs & derivatives, pharmacology)
• Carbon Dioxide (blood)
• Cerebrovascular Circulation (drug effects)
• Haplorhini
• Hypercapnia (enzymology)
• Male
• NG-Nitroarginine Methyl Ester
• Nitric Oxide Synthase
• Oxygen (blood)