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Selected Contribution: HSP20 phosphorylation in nitroglycerin- and forskolin-induced sustained reductions in swine carotid media tone

2001; American Physiological Society; Volume: 91; Issue: 3 Linguagem: Inglês

10.1152/jappl.2001.91.3.1460

8750-7587

Christopher M. Rembold, Matthew John O’Connor, Michael W. Clarkson, Robert L. Wardle, Richard A. Murphy,

Heart Rate Variability and Autonomic Control

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 Ca 2+ concentration ([Ca 2+ ] i ) and myosin regulatory light chain (MRLC) phosphorylation on serine (Ser)-19 (Ser 19 ). 2) The sustained inhibitory response is typically associated with Ser 16 phosphorylation of heat shock protein 20 (HSP20) without sustained reductions in [Ca 2+ ] i or MRLC phosphorylation. We investigated whether the extent of Ser 16 -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 Ser 16 -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 Ser 16 -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 Ser 16 -HSP20 phosphorylation without reductions in MRLC phosphorylation levels. Forskolin increased Ser 16 -HSP20 phosphorylation to a greater extent and inhibited force more completely than that observed with nitroglycerin. Increases in Ser 16 -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 Ser 16 -HSP20 phosphorylation may be a cyclic nucleotide-dependent, yet MRLC phosphorylation-independent, inhibitor of smooth muscle contractile force.