Sex-related Decrease In [Ca²⁺]_i Signaling And Ca²⁺-dependent Contraction In Inferior Vena Cava Of Female Rat

Objective:To investigate the sex difference in the [Ca2+]i signaling including the Ca2+ release mechanism from the intracellular stores and the Ca2+entry mechanisms as well as the Ca2+-dependent contraction in IVC of rat.Methods:IVC segments were incubated in Krebs solution containing the cell permeable Ca2+indicator fura-2/AM, Simultaneous measurement of isometric contraction and the 340/380 fluorescence ratio induced by PHE(10-5M), KCl (96mM) and AngⅡ(10-6M) were performed in IVC of male and female rats.Results:All the IVC tissue were successfully dissected and loaded with cell permeable Ca2+indicator fura-2/AM. In male IVC, phenylephrine (PHE; 10-5 M) caused significant increase in contraction and [Ca2+]i. In female IVC, PHE induced contraction was significantly reduced, but [Ca2+]i did not differ significantly from males. Membrane depolarization by KCl (96 mM), which stimulates Ca2+influx, caused parallel increases in contraction and [Ca2+]i in male IVC, and the KCl-induced contraction was significantly reduced in parallel with [Ca2+]i in female IVC.Conclusion:The reduced contraction, [Ca2+]i and [Ca2+]i sensitivity in female veins render them more prone to dilation. Objective:To investigate sex differences in venous endothelial function and the role of estrogen, estrogen receptors in venous function.Methods:The percentage of venous relaxation induced by Ach (10-5M), E2 (10-6M), ER-receptors including PPT(ER-αagonist,10-6M), DPN(ER-βagonist, 10-6M), and G1(GPR30-agonist, 10-6M) in IVC precontracted with PHE (10-5 M) was measured. Western Blot was applied in detecting the difference in ERs expression in IVC.Results:Ach induced relaxation was greater in female than male IVC. Either of E2, PPT, DPN or G1 caused venous relaxation in female IVC pretreated with PHE (10-5 M). The IVC relaxation induced by E2, DPN, and G1 were reversible, but the venorelaxant effect of PPT was irreversible. Western blot analysis of IVC tissue homogenate revealed that the amount of ERs (ER-a, ER-β,and GPR30) was significantly greater in female compared with male IVC.Conclusion:The enhanced endothelium-dependent vasodilation and increased ER expression/activity may result in reduced venous contraction in female rats. E2/ER-mediated venous relaxation in female rats could be prevented by NOS blockade, suggesting inhibition of an NO-dependent relaxation pathway. The reduced venous contraction and enhanced E2/ER-mediated venous relaxation give rise to more distensible veins in female rats.