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Am J Physiol Regul Integr Comp Physiol 286: R888-R893, 2004. First published January 8, 2004; doi:10.1152/ajpregu.00482.2003
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NEUROHUMORAL CONTROL OF CIRCULATION AND HYPERTENSION

Cytochrome P-450 metabolites in endothelin-stimulated cardiac hormone secretion

Sook Jeong Lee, Carol S. Landon, Stanley J. Nazian, and John R. Dietz

Department of Physiology and Biophysics and the University of South Florida, Cardiac Hormone Center, Tampa, Florida 33612

Submitted 22 August 2003 ; accepted in final form 6 January 2004

We examined the role of cytochrome P-450-arachidonate (CYP450-AA) metabolites in endothelin-1 (ET-1)-stimulated atrial natriuretic peptide (ANP) and pro-ANP-(1-30) secretion from the heart. 17-Octadecynoic acid (17-ODYA, 10-5 M) significantly inhibited ANP secretion stimulated by ET-1 (10-8 M) in the isolated perfused rat atria and inhibited pro-ANP-(1-30) secretion stimulated by ET-1 (10-8 M) or 20-hydroxyeicosatetraenoic acid in cultured neonatal rat ventricular myocytes (NRVM). In NRVM, 17-ODYA significantly (P < 0.05) increased secretion of cAMP but had no significant effect on the secretion of cGMP from NRVM. Staurosporine, an inhibitor of protein kinase C, completely blocked the inhibitory action of 17-ODYA, whereas a protein kinase A inhibitor, H-89 (5 x 10-5 M), did not significantly attenuate the effects of 17-ODYA. The results show that the inhibitory action of 17-ODYA on ET-1-augmented ANP secretion is mediated through cAMP and suggest that CYP450-AA may play an important role in ET-1-induced cardiac hormone secretion.

endothelin-1; 20-hydroxyeicosatetraenoic acid; 17-octadecynoic acid; nitric oxide; protein kinase A; protein kinase C; atrial natriuretic peptide; pro-ANP-(1-30); cardiac hypertrophy



Address for reprint requests and other correspondence: J. R. Dietz, Dept. of Physiology and Biophysics, Univ. of South Florida, College of Medicine, Box 8, Tampa, FL 33612 (E-mail: jdietz{at}hsc.usf.edu).




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