Effects of propranolol and L-NAME on β-adrenoceptor-mediated relaxation in rat carotid artery

1 The properties of beta-adrenoceptors mediating vascular relaxation in rat isolated carotid artery were investigated. Ring segments of arteries were preconstricted with the thromboxane A(2) receptor agonist U-46619 and relaxation to beta-adrenoceptor agonists determined. 2 Isoprenaline produced a concentration-dependent relaxation of U-44619-constricted arteries. The concentration-response curve (CRC) to isoprenaline was shifted to the right by propranolol (1 mu M) although the shift was less (105 fold; pA(2), 8.02) than would be expected for an effect of isoprenaline at classical P-adrenoceptors (300-1000 fold; pA(2), 8.5-9). L-NAME (100 mu M) significantly reduced responses to isoprenaline, lowering the slope of the CRC and reducing the maximum response. 3 The selective beta(3)-adrenoceptor agonists, BRL 37344 and ZD2079, also produced concentration-dependent relaxation of the arteries. L-NAME (100 mu M) shifted the BRL 37344 CRC to the right 15 fold with no reduction in the slope or maximum response. L-NAME (100 mu M) had no significant effect on the ZD2079 CRC. 4 In conclusion, relaxation to isoprenaline in rat carotid artery is inhibited by propranolol in a manner suggesting a mixed population of classical (beta(1)-/beta(2)-) and atypical (beta(3)-) adrenoceptors. The presence of beta(3)-adrenoceptors was confirmed by the relaxant effects of the selective beta(3)-adrenoceptor agonists BRL 37344 and ZD2079. L-NAME attenuated responses to both isoprenaline and the beta(3)- adrenoceptor agonist BRL 37344, suggesting a role for endothelial release of nitric oxide in beta-adrenoceptor mediated relaxation. However, the relaxant effect of BRL 37344 was attenuated by L-NAME to a lesser extent than that of isoprenaline. In addition, L-NAME had no effect on relaxation induced by ZD2079. These results suggest that there may be a differential contribution of endothelium to classical beta-and beta(3)-adrenoceptor-mediated effects, with endothelium contributing less to beta(3)-adrenoceptor-mediated relaxation.