Ca 2+ Sensitization Contributes to Myogenic Control of Arterial Diameter in Skeletal Muscle Resistance Arteries

Abstract

The myogenic response of resistance arteries to changes in intravascular pressure is a crucial determinant of peripheral vascular resistance. Ca2+ sensitization via inhibition of myosin light chain phosphatase (MLCP), due to phosphorylation of the MLCP targeting subunit 1 (MYPT1) by Rho-associated kinase (ROK), contributes to myogenic constriction of cerebral arteries. As it is unknown if this occurs in non-cerebral vessels we assessed the role of Ca2+ sensitization in the myogenic response of skeletal muscle arterioles (rat gracilis and cremaster). ROK inhibition with H1152 suppressed myogenic constriction between 40 and 120 mmHg. Increasing pressure from 10 to 80 mmHg caused an H1152-sensitive increase in MYPT1-T855 and myosin regulatory light chain (LC20) phosphorylation, but phospho-MYPT1-T697 and -CPI-17 levels were unchanged. Gracilis and cremaster arteries showed high basal levels of LC20 phosphorylation at 10 mmHg, comparable to the level in cerebral arteries at 60 mmHg. These findings suggest that Ca2+ sensitization contributes to the myogenic response of skeletal muscle resistance arteries. High basal LC20 phosphorylation may be the result of increased basal MYPT1 phosphorylation and indicates that myogenic constriction occurs over a narrow range of LC20 phosphorylation. (Support from CIHR MOP-97988 to WCC, AHFMR/CIHR to AEY and Spanish Ministry of Education & Science to OC).