Effects of maturation on mechanisms of cGMP-induced cerebral vasodilatation

In light of observations that cerebrovascular levels of cGMP vary during ma turation, the present study examines the possibility that the mechanisms me diating cGMP-induced cerebral vasodilatation also change during maturation. Specifically, these experiments explore age-related changes in the ability of cGMP to both: (1) depress cytosolic calcium concentration, and (2) atte nuate contractile protein calcium sensitivity in alpha -toxin and beta -esc in permeabilized preparations as well as fura-2 loaded arteries. The presen t data demonstrate that: (1) cGMP attenuates cytosolic calcium concentratio n at lower concentrations than required to reduce myofilament calcium sensi tivity; (2) both potassium-induced and 5HT-induced contractions were more s ensitive to cGMP in fetal than adult arteries; (3) all potassium-induced in creases in cytosolic calcium were resistant to the effects of cGMP, but tho se produced by 5HT were sensitive to attenuation by cGMP, and more so in fe tal than in adult basilar arteries, and (4) cGMP attenuated both basal and agonist-enhanced myofilament calcium sensitivity. Overall, these data demon strate that the mechanisms mediating the multiple vasoactive effects of cGM P are more potent in immature than in mature cerebral arteries and are heav ily influenced by both the artery type and the method of contraction. Copyr ight (C) 2001 S. Karger AG, Basel.