Steady-state dependence of stress on cross-bridge phosphorylation in the swine carotid media.

Tonic contractions of the swine carotid media are typically characterized by initial transients in myoplasmic [Ca2+] and cross-bridge phosphorylation followed by force maintenance with reduced intracellular [Ca2+] and cross-bridge phosphorylation ("latch"). The presence of effective mechanisms in the carotid media to limit steady-state myoplasmic [Ca2+] and cross-bridge phosphorylation to modest increases over resting values has limited experimental attempts to determine the dependence of active stress (force/tissue cross-sectional area) on cross-bridge phosphorylation. In this study, we employed stimulation protocols that combined effective contractile agonists with inhibitors of Ca2+ extrusion or sequestration to achieve high steady-state levels of cross-bridge phosphorylation (up to 60%). Increases in cross-bridge phosphorylation from 30 to 60% were not associated with significant increases in stress in agreement with the predictions of Hai and Murphy [Am. J. Physiol. 254 (Cell Physiol. 23): C99-C106, 1988] four-state cross-bridge model for the carotid media. Thus cross-bridge phosphorylation may suffice to determine force generation in vascular smooth muscle if both phosphorylated and dephosphorylated attached cross bridges (or latch bridges) contribute to active stress.