NEURONAL NOS-DERIVED NO PLAYS PERMISSIVE ROLE IN CEREBRAL BLOOD-FLOW RESPONSE TO HYPERCAPNIA

The aim of the present study was to determine whether neuronal nitric oxide synthase (nNOS)-derived nitric oxide (NO) plays a permissive rol e in the regulation of cerebral blood flow (CBF) response to hypercapn ia. To this end, we examined whether the administration of NO donors c ould reestablish the regional CBF (rCBF) response to hypercapnia after nNOS inhibition with 7-nitroindazole (7-NI). Rats were anesthetized w ith 1% halothane, and rCBF in the cortex was measured by laser-Doppler flowmetry. The administration of 7-NI (40 mg/kg ip) decreased resting rCBF by 17 +/- 5% (n = 6, P < 0.05) and attenuated the rCBF response to hypercapnia by 30 +/- 8% in comparison with the response seen in ra ts treated with the vehicle (peanut oil) alone. Intracerebroventricula r administration of NO donors, sodium nitroprusside (SNP; n = 7) and m ethylammoniohexyl)amino]}diazen-1-ium-1,2-diolate (MAHMA NONOate; n = 6) in a dose of 0.1-1 nmol/min after 7-NI restored both resting rCBF t o baseline and the vasodilatory response to hypercapnia. In contrast, intravenous infusion of SNP (0.05-0.5 nmol/min, n = 6) or intracerebro ventricular administration of an NO-independent vasodilator, the stabl e prostaglandin It analog iloprost (0.01-0.1 nmol/min, n = 6), after 7 -NI failed to restore the vasodilatory response to hypercapnia, despit e the fact that it restored the resting rCBF to baseline. nNOS activit y, assessed by the conversion of labeled arginine to citrulline, was i nhibited 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. They further indicate that the repletion of intraparenchymal NO allows the hypercapnic cere brocortical vasodilation to occur. Therefore, it is suggested that the nNOS-derived NO plays a permissive role in the CBF response to hyperc apnia.