Mechanisms of cGMP-induced cerebral vasodilatation: Contractile agonist and developmental age make a difference

In light of observations that maturation dramatically influences cerebrovascular metabolism of cGMP, the present study examines the hypothesis that the ability of cGMP to produce cerebral vasodilatation changes during maturation. Specifically, these experiments explore age-related changes in cGMP's ability to depress cytosolic calcium concentration and attenuate myofilament calcium sensitivity. The results obtained in α-toxin-permeabilized and Fura-2-loaded ovine basilar arteries demonstrate that cGMP produces relaxation by attenuating both the cytosolic calcium concentration and myofilament calcium sensitivity in ovine basilar arteries. More importantly, these findings reveal that the vasorelaxant potency and efficacy of cGMP are much greater in immature than in mature cerebral arteries. Together with the elevated levels of the cGMP characteristic of immature cerebral arteries, these data implicate cGMP as a major regulator of cerebrovascular tone in the immature cerebral circulation.