PHYSIOLOGICAL VARIATIONS IN-OVINE CEREBROVASCULAR CALCIUM SENSITIVITY

Cerebrovascular reactivity to biogenic amines varies in relation to bo th arterial diameter and age. The present study examines the hypothesi s that these patterns of reactivity are secondary to corresponding var iations in the Ca2+ sensitivity of the contractile proteins. To test t his hypothesis, we permeabilized segments of common carotid (Com), bas ilar, main branch middle cerebral, and second-branch middle cerebral ( MCA-B) arteries from nonpregnant adult and near-term fetal sheep using beta-escin. Permeabilization methods were carefully validated and adj usted for each artery type. Baseline myofilament Ca2+ sensitivity in b oth adults and fetuses increased significantly from the Com to the MCA -B and was generally higher in fetuses than in adults. Serotonin dose dependently increased Ca2+ sensitivity via a G protein-dependent mecha nism in all arteries. The magnitudes of this effect did not vary among artery types but were significantly greater in fetal than in adult ar teries. This effect of serotonin was mimicked by guanosine 5'-O-(3-thi otriphosphate), a nonhydrolyzable analog of guanosine 5'-triphosphate, and its effects were also much greater in fetal than in adult arterie s. We conclude that patterns of cerebrovascular reactivity to biogenic amines are determined, at least in part, by underlying variations in baseline myofilament Ca2+ sensitivity and/or its alteration by G prote in-dependent mechanisms.