Pressure-dependent myogenic constriction of cerebral arteries occurs independently of voltage-dependent activation

Pressure-induced decreases in arterial diameter are accompanied by membrane depolarization and Ca2+ entry via voltage-gated Ca2+ channels. Recent evidence also suggests the involvement of Ca2+ sensitization of the contractile proteins. Both PKC and Rho kinase are candidate second messengers for the mediation of the sensitization process. We investigated the signaling pathways of pressure-induced decreases in rat cerebral artery diameter in vessels that were depolarized with a 60 mM potassium-physiological salt solution (KPSS). Arteries were mounted on a pressure myograph, and pressure-induced constrictions were recorded. In some experiments simultaneous changes in intracellular Ca2+ concentration ([Ca2+](i)) were recorded by using fura 2 fluorescence photometry. Pressure increases induced constriction with significant changes in [Ca2+](i) at high pressures (60100 mmHg). The ratio of the change in diameter to change in [Ca2+](i) was greater for pressure-induced constriction compared with constriction produced by depolarization with 60 mM KPSS, suggesting that in addition to increases in [Ca2+](i), enhanced myofilament Ca2+ sensitivity occurs during pressure-induced decreases in arterial diameter. Depolarizing the membrane with 60 mM KPSS increased [Ca2+](i) via a Ca2+ influx pathway insensitive to PKC inhibition. Cerebral arteries were able to maintain their diameters in the continued presence of 60 mM KPSS. Pressure-induced constriction under these conditions was not associated with further increases in Ca2+ but was abolished by selective inhibitors of PLC, PKC, and Rho kinase. We report for the first time that in rat cerebral arteries, pressure-induced decreases in arterial diameter are not only due to increases in voltage-gated Ca2+ influx but also to accompanying increases in myofilament sensitivity to Ca2+ mediated by PKC/ Rho kinase activation.