Characterization of signal transduction events stimulated by 8-epi-prostaglandin(PG)F-2 alpha in rat aortic rings

One of the most abundant F-2 isoprostanes formed under pathological conditions is 8-epi-prostaglandin F-2 alpha (8-epi-PGF(2 alpha)), a potent vasoconstrictor. The purpose of this study was to determine the signal transduction events initiated by 8-epi-PGF(2 alpha)-induced vasoconstriction. isolated arterial rings from male Sprague-Dawley rats were suspended in tissue baths containing Krebs-Henseleit salt solution, stretched to optimal resting tension and stimulated, 8-epi-PGF(2 alpha) induced concentration-dependent contractions in pulmonary arteries (EC50; 7.7 +/- 2.1 mu M; n = 3) and aortas (EC50: 0.9 +/- 0.1 mu M; n = 4) which were blocked by the TXA(2) receptor antagonists SQ29548, L657925 and L657926. The contractile response to 8-epi-PGF(2 alpha) was significantly (*p < 0.05; n 4) diminished by: 2) indomethacin and ibuprofen; 2) Ca++ free media; 3) verapamil, a voltage gated Ca++ channel blocker; 4) flunarizine, a T-type Ca++ channel blocker; and 5) calphostin C, a protein kinase C inhibitor. These data suggest that the contractile response to 8-epi-PGF(2 alpha) is: 1) mediated via activation of TXA, receptors; 2) partially dependent on the synthesis and release of other cyclooxygenase derived products; 3) dependent on an influx of extracellular Ca++ possibly via Ca++ channels; and 4) may be PKC dependent.