REGULATION OF CA2-OVINE CEREBRAL-ARTERIES - EFFECTS OF ARTERY SIZE AND AGE( SENSITIZATION BY PKC AND RHO PROTEINS IN)

G protein-regulated Ca2+ sensitivity of vascular contractile proteins plays an important role in cerebrovascular reactivity. The present stu dy examines the intracellular mechanisms that govern G protein-regulat ed Ca2+ sensitivity in cerebral arteries of different size and age. We studied beta-escin-permeabilized segments of common carotid, basilar, and middle cerebral arteries from nonpregnant adult and near-term fet al sheep. Activation of protein kinase C (PKC) by (-)-indolactam V or a phorbol ester produced receptor-independent increases in Ca2+ sensit ivity. Such increases were more marked in immature arteries and were i nversely correlated with artery size in both mature and immature arter ies. However, inhibitors of PKC did not significantly affect increases in Ca2+ sensitivity in responses to either serotonin (5-hydroxytrypta mine, 5-HT) or guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S). Alte rnatively, deactivation of rho p21, a small G protein associated with Rho kinase, by exotoxin C3 fully prevented increases in Ca2+ sensitivi ty in responses to 5-HT or GTP gamma S in both adult and fetal arterie s of all types. Neither inhibitors of PKC nor exotoxin C3 altered base line Ca2+ sensitivity. We conclude that patterns of receptor- and/or G protein-mediated modulation of Ca2+ sensitivity are dependent on an i ntracellular pathway that involves activation of small G proteins and Rho kinase. In contrast, PKC has little, if any, role in agonist-induc ed Ca2+ sensitization under the present experimental conditions.