Faculty Collaboration Database

The role of nitric oxide in the cerebrovascular response to hypercapnia. Anesth Analg 1997 Feb;84(2):363-9

Date

02/01/1997

Pubmed ID

9024030

DOI

10.1097/00000539-199702000-00023

Scopus ID

2-s2.0-0031057266 (requires institutional sign-in at Scopus site)   23 Citations

Abstract

Laser Doppler flowmetry was used to further investigate the role of nitric oxide (NO) in CO2-induced cerebrocortical hyperemia in rats. A second objective was to elucidate the source(s) of the NO involved in the response to hypercapnia. We used the L-arginine analogue N omega-nitro-L-arginine methyl ester (L-NAME) to inhibit NO synthase (NOS) and 7-nitroindazole (7-NI) to selectively inhibit brain or nonendothelial NOS. Rats were anesthetized with a single dose of intraperitoneal (IP) pentobarbital (65 mg/kg) for surgery; 60-90 min later they were ventilated with 1.0% halothane in 30% O2 for 1 h to achieve a steady state. The animals were assigned to one of five groups. A control group (n = 9) was infused with 1 mL of saline. The second group (n = 10) received 20 mg/kg of L-NAME intravenously (IV). A third group (n = 9) also received L-NAME; in addition, cerebrocortical laser Doppler flow (LDF) and mean arterial pressure (MAP) were restored to baseline using the NO donor sodium nitroprusside (SNP). In a fourth group (n = 9), MAP was increased to the level usually seen after L-NAME with an infusion of phenylephrine (0.5-5 micrograms.kg-1.min-1). A fifth group (n = 11) received 7-NI at 40 mg/kg IP. The hypercapnic response of LDF was tested in all groups by adding 5% CO2 to the inspired gas at 30-45 min posttreatment; all changes in LDF were significant. In the control group, hypercapnia induced a 70% +/- 24% increase in LDF. In the L-NAME-treated group, the response was decreased to 36% +/- 22% at a posttreatment LDF that was 25% +/- 13% lower than the pre-L-NAME level. In the group where baseline LDF and MAP were restored with SNP, the CO2 response was 56% +/- 15% (not significant versus control). In the group in which MAP was increased with phenylephrine, the response to hypercapnia was 48% +/- 22% at a posttreatment LDF unchanged from pretreatment. These data suggest that increased vascular tone or the absence of basal NO after NOS inhibition influenced the vasodilator response to hypercapnia. In the 7-NI-treated group the response to hypercapnia was 38% +/- 3%, significantly attenuated at a posttreatment flow only 14% +/- 7% lower than pre-7-NI. We conclude that 1) endothelial NO does not mediate the response to hypercapnia but may have a permissive role in the response and 2) that brain NO may have an important role in response to hypercapnia.

Author List

Smith JJ, Lee JG, Hudetz AG, Hillard CJ, Bosnjak ZJ, Kampine JP

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Blood Pressure
Brain
Cerebrovascular Circulation
Enzyme Inhibitors
Hypercapnia
Indazoles
Laser-Doppler Flowmetry
Male
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase
Nitroprusside
Phenylephrine
Rats
Rats, Sprague-Dawley
Vasoconstrictor Agents
Vasodilator Agents