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

Add time:07/17/2019    Source:sciencedirect.com

1.1. 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).2.2. In isolated canine basilar artery (CBA), 8-Br-cGMP but not 8-Br-cAMP, significantly inhibited Ca2+-induced and agonist [serotonin(5-HT), prostaglandin(PG)F2α or endothelin]-induced contraction, in a concentration-dependent manner.3.3. 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 Ca2+-influx.4.4. Neither 8-Br-cGMP nor 8-Br-cAMP modified contraction induced by caffeine which elicits Ca2+ release from intracellular Ca2+ store.5.5. 8-Br-cGMP lowered the high K+-induced sustained [Ca2+] elevation.6.6. 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.

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