17beta-estradiol inhibits calcium-dependent and -independent contractions in isolated human saphenous vein.
Studies suggest that estrogen modulate vascular reactivity but at present its exact mechanism of action has yet to be clarified. The aim of this study was to evaluate the effect of 17beta-estradiol (E2) on calcium-dependent and -independent contractions induced in the human saphenous veins (HSVs). HSVs were obtained from patients undergoing coronary artery bypass graft surgery. The ability of E2 to modulate Ca(2+) entry was assessed by obtaining concentration-response curve to CaCl(2) in the absence or presence of E2. In other experiments intracellular Ca(2+) was depleted by repeated application of phenylephrine in the presence of cyclopiazonic acid (CPA). Then, at the plateau of PGF(2alpha) contraction, E2 or nifedipine (NIF) was added. Involvement of protein kinase C (PKC) in relaxant effect of E2 was evaluated by application of phorbol-12,13-dibutyrate (PDBu) in normal or Ca(2+)-free Krebs' solution. When the contraction was obtained, E2 or NIF was added. In Ca(2+)-free hyperpolarizing solution, pretreatment with E2, concentration dependently reduced contractions induced by cumulative addition of calcium chloride. Furthermore, E2 elicited relaxant effects on the PGF(2alpha)-induced contractions in Ca(2+)-free solution in the presence or absence of CPA. Both E2 and NIF produced significant relaxation in HSV rings contracted by direct activation of PKC in Krebs' solution. However, in Ca(2+)-free solution, NIF failed to induce relaxant effect but E2 kept its effect on the PDBu-induced contraction. These results suggest that the relaxant effect of E2 on HSV is elicited by calcium-dependent and -independent pathways. The calcium-independent pathway may involve PKC inhibition.
Babaei
Hossein
H
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. babaeih@tbzmed.ac.ir
Azarmi
Yadollah
Y
D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D012501:Saphenous Vein / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D015240:Phorbol 12,13-Dibutyrate; D004958:Estradiol; D002118:Calcium