Pelligrino. Possible obligatory functions of cyclic nucleotides in hypercapnia-induced cerebral vasodilation in adult rats. Am. J. Physiol. 276 (Heart Circ. Physiol. 45): H480-H487, 1999.-Current evidence suggests that nitric oxide (NO) and vasodilating prostanoids, possibly via the actions of cGMP and cAMP, play permissive roles in hypercapnic cerebral vasodilation. The present study examined whether cGMP and cAMP have obligatory functions in hypercapnia. Using a closed cranial window in adult rats, we measured pial arteriolar diameters and periarachnoid cerebrospinal fluid (pCSF) cyclic nucleotide levels during normo-and hypercapnia and in the presence or absence of inhibitors of neuronal NO synthase (nNOS) or cyclooxygenase (COX). Also, we measured cGMP and cAMP contents in primary neuronal and astrocyte cultures, at different levels of CO 2 . Hypercapnia (arterial PCO 2 65 mmHg)-induced pial arteriolar dilation was accompanied by 70-80% elevations in pCSF cGMP and cAMP. Inhibition of nNOS with 7-nitroindazole (7-NI) significantly reduced both the CO 2 -induced arteriolar dilation (by 77%) and the pCSF cGMP and cAMP increases (by 60-70%). Inhibition of COX with indomethacin reduced arteriolar CO 2 reactivity (by 83%) and pCSF cyclic nucleotide increases (by 80-100%). In neuronal cultures a transient NO-dependent increase in cGMP, but not cAMP, was seen when the CO 2 level was raised from 5 to 14%. No changes were seen in astrocytes. The 7-NI and indomethacin-inhibitable increases in pial arteriolar diameter and cyclic nucleotide production during hypercapnia suggest a link between these two responses. One possible, although not exclusive, interpretation of these findings is that the cyclic nucleotides have an obligatory function in the CO 2 response. The large overlap in the abilities of nNOS and COX inhibitors to elicit those effects further implies interactions (''cross talk'') between the cGMP and cAMP vasodilating pathways. The in vitro data suggest that hypercapnia stimulates NO production in neurons.
7-nitroindazole; indomethacin; astrocyte; neuron; primary culture; periarachnoid cerebrospinal fluidThe costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked ''advertisement'' in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.