Neuronal nos-derived no plays permissive role in cerebral blood
flow response to hypercapnia.
Okamoto, Hirotsugu, Antal G. Hudetz, Richard J. Roman, Zeljko J.
Bosnjak, John P. Kampine.
Departments of Anesthesiology and Physiology, Medical College of
Wisconsin, Milwaukee, Wisconsin, U.S.A.
APStracts 3:0342H, 1996.
The aim of the present study was to determine whether neuronal nitric
oxide synthase (nNOS)-derived nitric oxide (NO) played a permissive
role in the regulation of cerebral blood flow (CBF) response to
hypercapnia. To this end, we examined if the administration of NO
donors could re-establish the regional CBF (rCBF) response to
hypercapnia, following nNOS inhibition with 7-nitroindazole (7-NI).
Rats were anesthetized with 1% halothane and rCBF in the cortex was
measured by laser-Doppler flowmetry. The administration of 7-NI (40
mg/kg, i.p.) decreased resting rCBF by 17 5% ( SD, n=6, p<0.05) and
attenuated the rCBF response to hypercapnia by 30 8% in comparison to
the response seen in rats treated with the vehicle (peanut oil)
alone. Intracerebroventricular (i.c.v.) administration of NO donors,
SNP (n=7) and MAHMA NONOate (n=6) in a dose of 0.1-1 nmoles/min
following 7-NI restored both resting rCBF to baseline and
vasodilatory response to hypercapnia. In contrast, intravenous
infusion of sodium nitroprusside (SNP, 0.05-0.5 nmoles/min, n=6) or
i.c.v. administration of a NO-independent vasodilator, stable
prostaglandin I2 analogue Iloprost (0.01-0.1 nmoles/min, n=6)
following 7-NI failed to restore the vasodilatory response to
hypercapnia despite the fact that it restored the resting rCBF to
baseline. Neuronal NOS activity, assessed by the conversion of
labeled arginine to citrulline, was inhibited by 70 7% after the
administration of 7-NI. These findings confirm that the selective
inhibition of nNOS decreases resting rCBF and attenuates the rCBF
response of hypercapnia, and further indicate that the repletion of
intraparenchymal NO allows the hypercapnic cerebrocortical
vasodilation to occur. Therefore, it is suggested that the nNOS
-derived NO plays a permissive role in the cerebral blood flow
response to hypercapnia.
Received 22 April 1996; accepted in final form 23 July 1996.
APS Manuscript Number H358-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996