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Effects of formoterol and BRL 37344 on human umbilical arteries in vitro in normotensive and pre-eclamptic pregnancy. 2007

Baris Karadas, and Tijen Kaya, and Meral Cetin, and Ahmet Parlak, and Nedim Durmus, and Ihsan Bagcivan, and Sefa Gulturk
Department of Pharmacology, Izmir Ataturk Training and Research Hospital, 35360 Izmir, Turkey. bariskaradas@gmail.com

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.

UI MeSH Term Description Entries
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D011225 Pre-Eclampsia A complication of PREGNANCY, characterized by a complex of symptoms including maternal HYPERTENSION and PROTEINURIA with or without pathological EDEMA. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease. Toxemias, Pregnancy,EPH Complex,EPH Gestosis,EPH Toxemias,Edema-Proteinuria-Hypertension Gestosis,Gestosis, EPH,Hypertension-Edema-Proteinuria Gestosis,Preeclampsia,Preeclampsia Eclampsia 1,Pregnancy Toxemias,Proteinuria-Edema-Hypertension Gestosis,Toxemia Of Pregnancy,1, Preeclampsia Eclampsia,1s, Preeclampsia Eclampsia,EPH Toxemia,Eclampsia 1, Preeclampsia,Eclampsia 1s, Preeclampsia,Edema Proteinuria Hypertension Gestosis,Gestosis, Edema-Proteinuria-Hypertension,Gestosis, Hypertension-Edema-Proteinuria,Gestosis, Proteinuria-Edema-Hypertension,Hypertension Edema Proteinuria Gestosis,Of Pregnancies, Toxemia,Of Pregnancy, Toxemia,Pre Eclampsia,Preeclampsia Eclampsia 1s,Pregnancies, Toxemia Of,Pregnancy Toxemia,Pregnancy, Toxemia Of,Proteinuria Edema Hypertension Gestosis,Toxemia Of Pregnancies,Toxemia, EPH,Toxemia, Pregnancy,Toxemias, EPH
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D004983 Ethanolamines AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives. Aminoethanols
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000068759 Formoterol Fumarate An ADRENERGIC BETA-2 RECEPTOR AGONIST with a prolonged duration of action. It is used to manage ASTHMA and in the treatment of CHRONIC OBSTRUCTIVE PULMONARY DISEASE. 3-Formylamino-4-hydroxy-alpha-(N-1-methyl-2-p-methoxyphenethylaminomethyl)benzyl alcohol.hemifumarate,Arformoterol,BD 40A,Eformoterol,Foradil,Formoterol,Formoterol Fumarate, ((R*,R*)-(+-))-isomer,Formoterol, ((R*,R*)-(+-))-isomer,Oxis
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000318 Adrenergic beta-Agonists Drugs that selectively bind to and activate beta-adrenergic receptors. Adrenergic beta-Receptor Agonists,beta-Adrenergic Agonists,beta-Adrenergic Receptor Agonists,Adrenergic beta-Agonist,Adrenergic beta-Receptor Agonist,Betamimetics,Receptor Agonists, beta-Adrenergic,Receptors Agonists, Adrenergic beta,beta-Adrenergic Agonist,beta-Adrenergic Receptor Agonist,Adrenergic beta Agonist,Adrenergic beta Agonists,Adrenergic beta Receptor Agonist,Adrenergic beta Receptor Agonists,Agonist, Adrenergic beta-Receptor,Agonist, beta-Adrenergic,Agonist, beta-Adrenergic Receptor,Agonists, Adrenergic beta-Receptor,Agonists, beta-Adrenergic,Agonists, beta-Adrenergic Receptor,Receptor Agonist, beta-Adrenergic,Receptor Agonists, beta Adrenergic,beta Adrenergic Agonist,beta Adrenergic Agonists,beta Adrenergic Receptor Agonist,beta Adrenergic Receptor Agonists,beta-Agonist, Adrenergic,beta-Agonists, Adrenergic,beta-Receptor Agonist, Adrenergic,beta-Receptor Agonists, Adrenergic
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults

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