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

AbstractAlterations 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.
AuthorsBaris Karadas, Tijen Kaya, Meral Cetin, Ahmet Parlak, Nedim Durmus, Ihsan Bagcivan, Sefa Gulturk (Affiliation: Department of Pharmacology, Izmir Ataturk Training and Research Hospital, 35360 Izmir, Turkey. bariskaradas at gmail.com)
JournalVascular pharmacology (Vascul Pharmacol) Vol. 46 Issue 5 Pg. 360-6 (May 2007) ISSN: 1537-1891 United States
PMID17229593 (Publication Type: Comparative Study, In Vitro, Journal Article)
Chemical References
  • Adrenergic Antagonists
  • Adrenergic beta-Agonists
  • Ethanolamines
  • Receptors, Adrenergic, beta-2
  • Receptors, Adrenergic, beta-3
  • Vasodilator Agents
  • BRL 37344
  • Cyclic AMP
  • formoterol
Topics
  • Adrenergic Antagonists (pharmacology)
  • Adrenergic beta-Agonists (pharmacology)
  • Adult
  • Cyclic AMP (metabolism)
  • Ethanolamines (pharmacology)
  • Female
  • Humans
  • Muscle, Smooth, Vascular (drug effects, physiopathology)
  • Pre-Eclampsia (metabolism, physiopathology)
  • Pregnancy
  • Receptors, Adrenergic, beta-2 (drug effects, metabolism)
  • Receptors, Adrenergic, beta-3 (drug effects, metabolism)
  • Umbilical Arteries (drug effects, metabolism, physiopathology)
  • Vasodilation (drug effects)
  • Vasodilator Agents (pharmacology)