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Title: Cyclic GMP-induced reduction in cardiac myocyte function is partially mediated by activation of the sarcoplasmic reticulum Ca(2+)-ATPase. Author: Zhang Q, Yan L, Weiss HR, Scholz PM. Journal: Pharmacology; 2002 Feb; 64(2):106-12. PubMed ID: 11803251. Abstract: We tested the hypothesis that the mechanism through which cyclic GMP reduces cardiac function is mediated by activation of the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA). Cardiac myocytes were isolated from New Zealand white rabbits (n = 11). Individual ventricular cells were stimulated by electrical field stimulation. The maximal rate of cell shortening and percentage shortening were measured with a video edge detector. Thapsigargin (10(-8) mol/l) was used as a specific inhibitor of SERCA. When 8-bromo-cyclic GMP (8-Br-cGMP, 10(-7, -6, -5) mol/l) was added to cells, the maximal rate of myocyte shortening (R(max), microm/s) and percentage shortening were both decreased in a concentration-dependent manner. R(max) decreased 27% from 117 +/- 12 at baseline to 85.2 +/- 13 when 10(-5) mol/l of 8-Br-cGMP was present, and percent shortening was reduced 28% from 6.0 +/- 0.5 to 4.3 +/- 0.5%. Thapsigargin (10(-8) mol/l) increased the maximal rate of myocyte shortening and percent shortening. Addition of thapsigargin prior to 8-Br-cGMP reduced the negative effects of cGMP on myocyte function. The percent shortening decreased only 11% and R(max) decreased 14% with 10(-5) mol/l 8-Br-cGMP, which was not significant. Cyclopiazonic acid, another SERCA inhibitor, was also used to test whether 8-Br-cGMP reduced myocyte function through SERCA. The results were similar to those when thapsigargin was used. These results indicated that the cyclic GMP-induced reduction in cardiac myocyte function was partially mediated through the action of the sarcoplasmic reticulum Ca(2+)-ATPase.[Abstract] [Full Text] [Related] [New Search]