title: Cyclic nucleotide dependent relaxation in vascular smooth muscle.
abstract: Although not without controversy, the mechanisms inducing contraction of vascular smooth muscle are relatively well defined. There is a stimulus-induced increase in myoplasmic [Ca2+] with activation of myosin light chain kinase by the Ca(2+)-calmodulin complex, phosphorylation of the 20-kDa regulatory light chain of myosin, with subsequent cross-bridge cycling and force development. Ca(2+)-dependent phosphorylation of the myosin regulatory light chain appears to be the primary mechanism responsible for regulating stress in vascular smooth muscle. The relationship between myoplasmic [Ca2+] and myosin phosphorylation (i.e., the calcium sensitivity of phosphorylation) is regulated. It is higher with agonist stimulation than in tissues depolarized with high potassium solutions or after skinning procedures. The relationship between myosin phosphorylation and stress appears to be invariant with physiologic stimulation. This suggests that cross-bridge phosphorylation normally determines contraction. The mechanisms of relaxation are less well defined. In the most simple scheme, reduction of myoplasmic [Ca2+] with a fall in myosin light chain kinase activity would suffice to account for dephosphorylation of the regulatory light chain and relaxation. However, other mechanisms have been implicated in cyclic nucleotide dependent relaxation in vascular and other smooth muscle tissues. The current hypotheses of the mechanism of cyclic nucleotide dependent relaxation in vascular smooth muscle are reviewed.
authors.affiliation: Department of Pediatrics, Internal Medicine (Cardiology), and Physiology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: McDaniel
authors.forename: C M
authors.initials: CM
authors.lastname: Rembold
authors.forename: R A
authors.initials: RA
authors.lastname: Murphy
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D006801:Humans; D009126:Muscle Relaxation / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*
chemical_list: D000242:Cyclic AMP; D006152:Cyclic GMP