Effects of formoterol and BRL 37344 on human umbilical arteries in vitro in normotensive and pre-eclamptic pregnancy

Abstract

Alterations in vascular responses to β-adrenoceptor agonists in normotensive pregnancy and pre-eclampsia are not fully understood. Thus, we studied changes in vasodilator responses to β 2-adrenoceptor agonist formoterol and β 3-adrenoceptor 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 (β 1, β 2, β 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 mol/L) 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 p D 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 37344 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 β 2- and β 3-adrenoceptor subtypes, with contribution of cAMP. Umbilical arteries from subjects with pre-eclampsia showed a weaker β 2- and β 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.