Rapid inhibition of the contraction of rat tail artery by progesterone is mediated by inhibition of calcium currents

Abstract

Progesterone induced rapid relaxation of KCl-contracted tail artery helical strips from rats. The effect was dose dependent, with an IC50 (inhibitory concentration which produces 50% of the maximal response) of 8.9 microM progesterone. The actions of progesterone were not blocked by bicuculline, indicating that in this tissue the non-genomic actions of progesterone were not mediated via a gamma-aminobutyric acid (GABA)-A receptor. Fura-2 was used to measure intracellular calcium levels ([Ca(2+)](i)) in isolated vascular smooth muscle cells (VSMC). Incubation of cultured VSMC for 15 min with progesterone (10 microM) resulted in an inhibition of the KCl-induced [Ca(2+)](i )increase. The whole-cell patch-clamp technique was used to examine Ca(2+)-channel currents in the membrane of isolated VSMC. Progesterone suppressed the L-type Ca(2+)-channel currents in cells held at a potential of -40 mV. The effects of progesterone were quickly reversed by washout in all three experimental protocols suggesting that these effects on vascular tissues are non-genomic. The correlation of the effects on all these preparations, their time course and reversibility suggested that the rapid relaxation of the rat tail artery induced by progesterone is mediated at least in part by inhibition of L-type calcium channels, leading to inhibition of calcium responses in the VSMC of this tissue.

Non-genomic vasorelaxant effects of 17β-estradiol and progesterone in rat aorta are mediated by L-type Ca2+ current inhibition

“…Our results showed a more powerful effect of PRG than βES at high concentrations (100 μmol/L). The inhibition of LTCC current by PRG in A7r5 cells is here reported for the first time, although Zhang et al observed in rat tail vascular smooth muscle cells that PRG reduced the LTCC [25] . We already studied the effect of PRG and βES on the BAY-stimulated I Ca,L .…”

“…[20] . Some authors showed that the inhibition of Ca 2+ channels is associated to the vasodilatation mediated by estrogens [21][22][23] and PRG [24,25] . The effects of βES and PRG on VOCCs were the objective of some studies.…”

The modulatory role of androgens and progestins in the induction of vasorelaxation in human umbilical artery

“…Thus, the vasorelaxing effect to sex steroids could be due, at least in part, to inhibition of L-type Ca 2+ channels (Zhang et al, 1994(Zhang et al, , 2002Scragg et al, 2004) and/or activation of K + channels (Deenadayalu et al, 2001). However, our results showing that steroids-induced vasorelaxation was not affected by inhibitors of BK Ca , K v and K ATP channels rules out the involvement of K + channels.…”

“…This is, to the best of our knowledge, the first functional line of evidence describing the relaxant effects of 5-reduced androgens and progestins on vascular tone of HUA which may represent a potential regulatory role on fetoplacental blood flow. Accordingly, other studies have also reported the vasorelaxing properties of female and male sex steroids in experimental animals (Mendelsohn and Karas, 1999;Zhang et al, 2002;Perusquía, 2003). Likewise, μM concentrations of 17β-estradiol and progesterone induce a vasorelaxing effect in the isolated human coronary, mammary, placental and omental arteries (Omar et al, 1995;Belfort et al, 1996;Mugge et al, 1997;Ramírez et al, 1998).…”

“…These divergent results may be due to species differences, the vascular bed under study and/or the experimental conditions. Moreover, two main modes of action might help to explain the vasorelaxing response to male and female sex steroids, namely: (i) the control of [Ca 2+ ] i homeostasis, including inactivation of Ca 2+ entry via voltagegated (Zhang et al, 1994(Zhang et al, , 2002Scragg et al, 2004) and Life Sciences 81 (2007) 993 -1002 www.elsevier.com/locate/lifescie nonvoltage-gated pathways (Jones et al, 2002); and/or (ii) the activation of K + channels (Deenadayalu et al, 2001;Ding and Stallone, 2001), principally on the large-conductance Ca 2+ -activated K + channels (BK Ca ), voltage-dependent K + channels (K v ) and adenosine triphosphate (ATP)-sensitive K + channels (K ATP ). Hence, we set out to investigate the direct effect of a wide series of sex steroids, including dehydroepiandrosterone (DHEA), testosterone, progesterone and their 5-reduced metabolites, on the vascular tone of the human umbilical artery (HUA).…”