Role of beta2-adrenoceptors (beta-AR), but not beta1-, beta3-AR and endothelial nitric oxide, in beta-AR-mediated relaxation of rat intrapulmonary artery.
The aim of this study was to analyze beta-adrenoceptor (beta-AR)-mediated relaxation in rat intralobar pulmonary artery. The relaxant responses of beta-AR agonists were characterized using beta-AR antagonists in prostaglandin F2alpha (PGF2alpha)-precontracted arteries. The role of nitric oxide (NO) and endothelium in beta-AR-mediated relaxation was also investigated. Isoprenaline (a non-selective beta-AR agonist) and salbutamol (a selective beta2-AR agonist) induced vasorelaxation. ICI 118551 (a selective beta2-AR antagonist) antagonized the effect of both isoprenaline and salbutamol (pA2 values of 9.57 and 9.51 respectively). In contrast, atenolol (1 microM) and CGP 20712A (0.1 microM), two beta1-AR antagonists, did not modify the relaxing effect of isoprenaline. The response to isoprenaline obtained in the presence of nadolol (10 microM, a beta1/beta2-AR antagonist) was not further inhibited by SR 59230A (1 microM, a selective beta3-AR antagonist). The non-beta1/beta2-AR agonists studied (BRL 37344, SR 58611A, and CGP 12177A) did not elicit vasorelaxation. Relaxation to isoprenaline and salbutamol was unaffected by L-N(G)-nitro-arginine methyl ester (100 microM, an inhibitor of NO synthase) or after endothelium removal. These results demonstrate the role of beta2-AR in mediating relaxation in rat intralobar pulmonary artery precontracted with PGF2alpha. They indicate that beta2-AR-mediated relaxation in this artery is NO- and endothelium-independent. Furthermore, they do not provide evidence of a relaxant role of either beta1- or beta3-AR in PGF2alpha-precontracted rat intrapulmonary artery.
Pourageaud
Fabrice
F
Laboratoire de Pharmacologie de la Faculté de Pharmacie, INSERM EMI-0356, Université Victor Segalen Bordeaux 2, Casier 83, 146 rue Léo Saignat, 33076, Bordeaux cedex, France. fabrice.pourageaud@phcodyn.u-bordeaux2.fr
Leblais
Véronique
V
Bellance
Nadège
N
Marthan
Roger
R
Muller
Bernard
B
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011412:Propanolamines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000032:analysis / Q000187:drug effects; D018343:Receptors, Adrenergic, beta-2 / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3 / Q000032:analysis / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; D009569:Nitric Oxide; C026777:ICI 118551; D001262:Atenolol; D019001:Nitric Oxide Synthase; D007545:Isoproterenol; D000420:Albuterol; D019331:NG-Nitroarginine Methyl Ester