Functional roles of cyclic guanosine 3',5'-monophosphate analogue in cerebral vasodilation

1. Vasodilating effects of cyclic nucleotides in cerebral vasculature were examined using membrane permeable cyclic nucleotide analogues, 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) and 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP). 2. In isolated canine basilar artery (CBA), 8-Br-cGMP but not 8-Br-cAMP, significantly inhibited Ca(2+)-induced and agonist [serotonin(5-HT), prostaglandin(PG)F2 alpha or endothelin]-induced contraction, in a concentration-dependent manner. 3. When Ca2+ was depleted from intracellular store sites by pretreatment with A23187, 8-Br-cGMP but not 8-Br-cAMP strongly attenuated contractions induced by Ca(2+)-influx. 4. Neither 8-Br-cGMP nor 8-Br-cAMP modified contraction induced by caffeine which elicits Ca2+ release from intracellular Ca2+ store. 5. 8-Br-cGMP lowered the high K(+)-induced sustained [Ca2+]i elevation. 6. These results suggest that, at least in CBA, cGMP exerts its inhibitory effect on the contraction induced by influx of Ca2+, by reducing the level of [Ca2+]i and reducing [Ca2+]i sensitivity of the contractile machinery.