Effects of formoterol and BRL 37344 on human umbilical arteries in vitro in normotensive and pre-eclamptic pregnancy
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Alterations in vascular responses to beta-adrenoceptor agonists in normotensive pregnancy and pre-eclampsia are not fully understood. Thus, we studied changes in vasodilator responses to beta(2)-adrenoceptor agonist formoterol and beta(3)-adrcnoceptor agonist BRL 37344 on umbilical arteries isolated from normotensive (n = 12) and pre-eclamptic (n = 12) pregnant women. Changes in the relaxant effect of formoterol and BRL 37344 were investigated by measuring isometric tensions in endothelium-denuded strips of umbilical arteries in the presence or absence of metoprolol, ICI 118.551 and SR 59230A (beta(1), beta(2), beta(3)-adrenoceptor antagonists, respectively, 10(-6) mol/L). Effects of formoterol and BRL 37344 on cAMP levels of umbilical arteries were evaluated by radioimmunoassay kits. Formoterol (10(-10)-10(-4) mol/L) and BRL 37344 (10(-10)-10(-4) men) caused concentration-dependent relaxation of the contraction induced by phenylephrine (10(-5) mol/L) in umbilical artery strips isolated from both groups. E-max values of formoterol and BRL 37344 (for normotensive pregnant women: 87.33 +/- 0.87 and 53.25 +/- 1.17 vs. for pre-eclampsia: 73.68 +/- 1.58 and 43.64 +/- 1.19, n=12, P > 0.05, respectively) were significantly smaller in strips from pre-eclamptic women (P < 0.05), with no significant change in pD(2) values. E-max values of formoterol were significantly higher than those of BRL 37344 in both tissue (P < 0.05). ICI 118.551 and SR 59230A, but not metoprolol, antagonized the relaxant effects of formoterol and of BRL 2,7344 on umbilical artery strips isolated from normotensive and pre-eclamptic pregnant women. Formoterol and BRL 37344 increased cAMP levels in both groups, but less significant in pre-eclamptic strips (P < 0.05). These results suggest that the relaxation caused in human umbilical arteries by formoterol and BRL 37344 is mediated by a mixed population of beta(2)- and beta(3)-adrenoccptor subtypes, with contribution of cAMP. Umbilical arteries from subjects with pre-eclampsia showed a weaker beta(2)- and beta(3)-receptor-mediated relaxation to formoterol and BRL 37344, suggesting that the reduced action of formoterol and BRL 37344 may be partly due to a decreased effect of cAMP. (c) 2007 Elsevier Inc. All rights reserved.