Enhanced relaxation of porcine coronary arteries after acute exposure to aphysiological level of 17 beta-estradiol involves non-genomic mechanisms and the cyclic AMP cascade

1 The present study extends our previous finding that the endothelium-indep endent relaxation in porcine coronary artery rings is enhanced after short- term (20 min) exposure to a physiological concentration (1 nM) of 17 beta-e stradiol and demonstrates that this effect may be attributable to activatio n of the cyclic AMP pathway. 2 Isometric tension was recorded in isolated rings of porcine coronary arte ries. 3 Relaxation by levcromakalim and sodium nitroprusside, but not bradykinin and calcium ionophore A23187, were significantly potentiated following 20 m in treatment with 1 nM 17 beta-estradiol. This enhancing effect was insensi tive to the transcriptional and translational inhibitors, actinomycin D and cycloheximide respectively and absent following repeated washing of the ri ngs prior to construction of relaxation-response curves. 4 The potentiating actions of 1 nM 17 beta-estradiol on endothelium-indepen dent relaxation were mimicked by the cyclic AMP analogue 8-Bromo-cyclic AMP and the protein kinase A activator Sp-cyclic AMPS but not by the cyclic GM P analogue 8-Bromo-cyclic GMP. The modulatory effect of 17 beta-estradiol w as increased in the presence of the phosphodiesterase inhibitor 3-isobutyl- 1-methylxanthine. 5 The cyclic AMP-dependent protein kinase A inhibitor Rp-cyclic AMPS, but n ot the cyclic GMP antagonist Rp-8-Bromo-cyclic GMPS, effectively inhibited the enhancing effects 1M 17 beta-estradiol had on the relaxation responses of levcromakalim and sodium nitroprusside. 6 These data support our earlier findings that physiologically relevant con centrations of 17 beta-estradiol can acutely modify vasorelaxation in vitro . Furthermore, we report that this short-term effect of 17 beta-estradiol o n vasorelaxation appears to be mediated via non-genomic pathways and involv es the cyclic AMP cascade.