iloprost and 7-nitroindazole

The aim of the present study was to determine whether neuronal nitric oxide synthase (nNOS)-derived nitric oxide (NO) plays a permissive role in the regulation of cerebral blood flow (CBF) response to hypercapnia. To this end, we examined whether the administration of NO donors could reestablish the regional CBF (rCBF) response to hypercapnia after 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 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 rats treated with the vehicle (peanut oil) alone. Intracerebroventricular administration of NO donors, sodium nitroprusside (SNP; n = 7) and (Z)-1-[N-methyl-N-[6(N-methylammoniohexyl)aminol]]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 to baseline and the vasodilatory response to hypercapnia. In contrast, intravenous infusion of SNP (0.05-0.5 nmol/min, n = 6) or intracerebroventricular administration of an NO-independent vasodilator, the stable prostaglandin I2 analog iloprost (0.01-0.1 nmol/min, n = 6), after 7-NI failed to restore the vasodilatory response to hypercapnia, despite the fact that it restored the resting rCBF to baseline. nNOS 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. They 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 CBF response to hypercapnia.

Topics: Animals; Cerebrovascular Circulation; Enzyme Inhibitors; Epoprostenol; Hypercapnia; Iloprost; Indazoles; Laser-Doppler Flowmetry; Male; Neurons; Nitric Oxide; Nitric Oxide Synthase; Rats; Rats, Sprague-Dawley; Reference Values; Vasodilator Agents