17β-Estradiol inhibits calcium-dependent, but not calcium-independent, contraction in isolated rat aorta

It is now well known that 17β-estradiol has an endothelium- independent, non-genomic vasorelaxant effect. We hypothesized that 17β-estradiol has its non-genomic effect on calcium-independent contraction in de-endothelialized rat aortic rings. Rat aortic ring preparations were mounted in organ baths and exposed to contractile agents. 17β-Estradiol (8, 20 or 50 μM), but not 17α-estradiol, concentration-dependently decreased the tension induced by 1.0 μM phenylephrine (PE) in the presence, but not in the absence, of calcium in the solution. Pretreatment with 17β-estradiol concentration-dependently inhibited vascular contractions induced by cumulative addition of PE or calcium and almost completely abolished those induced by cumulative addition of Bay K8644, a calcium channel opener. Furthermore, 17β-estradiol also concentration-dependently decreased the tension induced by 0.3 μM phorbol 12,13-dibutyrate (PDBu), a protein kinase C activator, in the presence of calcium in the solution, but not in the absence of calcium in the solution. Pretreatment with 17β-estradiol had little effect on vascular contractions induced by PDBu or PE or on PE-induced mitogen-activated protein kinase (MAPK) activation in calcium-free Krebs solution. These results suggest that 17β-estradiol inhibits calcium-dependent, but not calcium-independent, vascular contraction.