Selected Contribution: HSP20 phosphorylation in nitroglycerin- and forskolin- induced sustained reductions in swine carotid media tone. Rembold, Christopher M., Matthew O'Connor, Michael Clarkson, Robert L. Wardle, and Richard A. Murphy. 1Cardiovascular Division, Department of Internal Medicine, and 2Department of Molecular Physiology and Biological Physics, University of Virginia Health System, Charlottesville, Virginia 22908
APStracts 8:0314A, 2001.
Cyclic nucleotide-induced relaxation of maximally activated arterial smooth muscle has two phases. 1) The initial relaxation transient is typically characterized by a rapid reduction in force associated with brief reductions in myoplasmic Ca2+ concentration ([Ca2+]i) and myosin regulatory light chain (MRLC) phosphorylation on serine (Ser)-19 (Ser19). 2) The sustained inhibitory response is typically associated with Ser16 phosphorylation of heat shock protein 20 (HSP20) without sustained reductions in [Ca2+]i or MRLC phosphorylation. We investigated whether the extent of Ser16-HSP20 phosphorylation quantitatively correlated with the sustained inhibitory response. With addition of nitroglycerin to histamine-stimulated swine carotid media, the initial relaxation transient was associated with a decrease in MRLC phosphorylation without an increase in Ser16-HSP20 phosphorylation. During the sustained phase of nitroglycerin- induced relaxation and during force redevelopment induced by washout of nitroglycerin in the continued presence of histamine, the level of Ser16-HSP20 phosphorylation, but not MRLC phosphorylation, correlated with inhibition of force. Forskolin, which increases cAMP concentration, also induced a sustained inhibitory response that was associated with increases in Ser16-HSP20 phosphorylation without reductions in MRLC phosphorylation levels. Forskolin increased Ser16-HSP20 phosphorylation to a greater extent and inhibited force more completely than that observed with nitroglycerin. Increases in Ser16-HSP20 phosphorylation correlated with the degree of force inhibition regardless of whether the relaxation was induced by nitroglycerin or forskolin. These data are consistent with the hypothesis that Ser16-HSP20 phosphorylation may be a cyclic nucleotide-dependent, yet MRLC phosphorylation-independent, inhibitor of smooth muscle contractile force. 

Received 3 April 2001; accepted in final form 16 May 2001
APS Manuscript Number A312-1.
Article publication pending J Appl Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 29 June 2001