| pA2 online © Copyright 2004 The British Pharmacological Society |
103P
University of Newcastle Winter Meeting December 2004 |
Involvement of NOS-3 in relaxations to beta-adrenoceptor agonists in mouse mesenteric artery K Al Zubair, S. Bexis & J.R. Docherty. Department of Physiology, Royal College of Surgeons in Ireland, 123 St. Stephen’s Green, Dublin 2, Ireland. |
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Print abstractVascular relaxations to beta-adrenoceptor agonists can involve beta1, beta2- or beta3-adrenoceptors and may involve endothelium derived NO, at least in some blood vessels ;(see Guimaraes & Moura, 2001). In this study, we have investigated relaxations to beta-adrenoceptor agonists in mesenteric artery from wild type (WT) and NOS-3-KO (knockout) mice.
Mesenteric and aortic arterial rings from C57-BL/6 WT and NOS-3-KO (Jackson Labs, USA) mice (22-28g female) were set up in small vessel myographs, at 37 °C in Krebs-Henseleit solution of the following composition (mM): NaCl 119, NaHCO3 25, D-glucose 11.1, KCl 4.7, CaCl2 2.5, KH2PO4 1.2, MgSO4 1.0, EDTA 0.03, ascorbic acid 0.28. Tissues were contracted with KCl (40 mM) and relaxed with the beta-adrenoceptor agonists isoprenaline (non-selective), formoterol (beta2-selective) and BRL 37344 (beta3- selective) in the presence of distilled water vehicle or antagonists (30 min exposure prior to agonist addition).
In mouse aorta, isoprenaline (0.001-100µM) failed to relax KCl (40mM) induced contractions.
In mesenteric artery from WT mice, KCl (40 mM) produced a contraction of 2.18±0.17 mN (mean ±S.E.M., n=35). Isoprenaline produced a concentration-dependent relaxation over the range 0.01-100 µM, with a maximum relaxation (100 µM) of 50.0±7.8% (n=6). Formoterol and BRL 37344 were much less potent than isoprenaline at producing relaxations, with maximum relaxations (100 µM) of 29.6±5.6% (n=7) and 20.8±10.4% (n=6), respectively. The alpha1-adrenoceptior antagonist prazosin (0.1 µM) did not alter the relaxations to isoprenaline. Relaxations to isoprenaline were abolished by the beta1-adrenoceptor selective antagonist atenolol (1 µM).
In mesenteric artery from NOS-3-KO mice, KCl (40 mM) produced a contraction of 2.54±0.24 mN (n=20). Isoprenaline failed to produce relaxations. In NOS-3-KO mice, formoterol and BRL 37344 (both 100 µM) produced small relaxations of 19.0±6.1% (n=5) and 12.8±4.8% (n=5), respectively.
It is concluded that beta-adrenoceptor mediated relaxations in mouse mesenteric artery predominantly involve beta1-adrenoceptors and NOS-3 mediated release of nitric oxide.
Guimaraes, S. & Moura, D. (2001) Pharmacol. Rev. 53, 319-356.