Karadas Baris, Kaya Tijen, Cetin Meral, Parlak Ahmet, Durmus Nedim, Bagcivan Ihsan, Gulturk Sefa
Department of Pharmacology, Izmir Ataturk Training and Research Hospital, 35360 Izmir, Turkey.
Vascul Pharmacol. 2007 May;46(5):360-6. doi: 10.1016/j.vph.2006.12.002. Epub 2006 Dec 8.
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)-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 (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) 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 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 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 beta(2)- and beta(3)-adrenoceptor 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.
正常妊娠和先兆子痫时血管对β-肾上腺素能受体激动剂反应的改变尚未完全明确。因此，我们研究了从正常血压（n = 12）和先兆子痫（n = 12）孕妇分离的脐动脉对β₂-肾上腺素能受体激动剂福莫特罗和β₃-肾上腺素能受体激动剂BRL 37344的血管舒张反应变化。通过测量在有无美托洛尔、ICI 118.551和SR 59230A（分别为β₁、β₂、β₃-肾上腺素能受体拮抗剂，10⁻⁶mol/L）存在下脐动脉去内皮条带的等长张力，研究福莫特罗和BRL 37344舒张作用的变化。用放射免疫分析试剂盒评估福莫特罗和BRL 37344对脐动脉cAMP水平的影响。福莫特罗（10⁻¹⁰ - 10⁻⁴mol/L）和BRL 37344（10⁻¹⁰ - 10⁻⁴mol/L）使两组分离的脐动脉条带中去氧肾上腺素（10⁻⁵mol/L）诱导的收缩呈浓度依赖性舒张。福莫特罗和BRL 37344的E(max)值（正常血压孕妇：87.33±0.87和53.25±1.17，先兆子痫孕妇：73.68±1.58和43.64±1.19，n = 12，P均>0.05）在先兆子痫孕妇的条带中显著较小（P<0.05），pD₂值无显著变化。在两种组织中，福莫特罗的E(max)值均显著高于BRL 37344（P<0.05）。ICI 118.551和SR 59230A而非美托洛尔可拮抗福莫特罗和BRL 37344对从正常血压和先兆子痫孕妇分离的脐动脉条带的舒张作用。福莫特罗和BRL 37344均使两组cAMP水平升高，但在先兆子痫条带中升高幅度较小（P<0.05）。这些结果表明，福莫特罗和BRL 37344在人脐动脉中引起的舒张是由β₂-和β₃-肾上腺素能受体亚型混合介导的，且有cAMP参与。先兆子痫患者的脐动脉对福莫特罗和BRL 37344的β₂-和β₃-受体介导的舒张作用较弱，提示福莫特罗和BRL 37344作用减弱可能部分归因于cAMP作用降低。
