Acute impairment of contractile responses by 17β-estradiol is cAMP and protein kinase G dependent in vascular smooth muscle cells of the porcine coronary arteries

Abstract

1 The aim of the present study was to investigate the involvement of adenosine 3′, 5′-cyclic monophosphate (cAMP) cascade in the acute impairment of contraction by 17β-estradiol in porcine coronary arteries, and to elucidate the signaling pathway leading to the activation of this cascade by the hormone. 2 Isometric tension was recorded in isolated rings of porcine coronary arteries. 3 The contraction to U46619 was reduced significantly following 30 min incubation with 1 nM 17β-estradiol or 1 nM isoproterenol. There was no additive effect when 17β-estradiol and isoproterenol were administered together. The effect of 17β-estradiol was mimicked by both the cyclic AMP analogue 8-Br-cAMP and the guanosine 3′,5′-cyclic monophosphate (cyclic GMP) analogue 8-Br-cGMP. 4 In rings with and without endothelium, the modulatory effect of 17β-estradiol was abolished by the adenylyl cyclase inhibitor, SQ 22536, but was unaffected by the guanylyl cyclase inhibitor, ODQ. 5 Both the cAMP antagonist Rp-8-Br-cAMPS and the cGMP antagonist inhibitor Rp-8-Br-cGMPS inhibited the effect of 17β-estradiol. 6 The effect of 17β-estradiol was unaffected by the protein kinase A inhibitor, KT5720, but was abolished by the protein kinase G (PKG) inhibitor, KT5823, which also abolished the effect of isoproterenol. 7 These data support our earlier findings that 17β-estradiol (1nM) acutely impairs contractile responses of porcine coronary arteries in vitro. This acute effect of 17β-estradiol involves cAMP in vascular smooth muscles and the activation of PKG.