Effects of propranolol and L-NAME on beta-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 A2 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 microM) although the shift was less (105 fold; pA2, 8.02) than would be expected for an effect of isoprenaline at classical beta-adrenoceptors (300-1000 fold; pA2, 8.5-9). L-NAME (100 microM) significantly reduced responses to isoprenaline, lowering the slope of the CRC and reducing the maximum response. 3. The selective beta3-adrenoceptor agonists, BRL 37344 and ZD2079, also produced concentration-dependent relaxation of the arteries. L-NAME (100 microM) shifted the BRL 37344 CRC to the right 15 fold with no reduction in the slope or maximum response. L-NAME (100 microM) 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 (beta1-/beta2-) and atypical (beta3-) adrenoceptors. The presence of beta3-adrenoceptors was confirmed by the relaxant effects of the selective beta3-adrenoceptor agonists BRL 37344 and ZD2079. L-NAME attenuated responses to both isoprenaline and the beta3-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 beta3-adrenoceptor-mediated effects, with endothelium contributing less to beta3-adrenoceptor-mediated relaxation.
MacDonald
A
A
School of Biological and Biomedical Sciences, Glasgow Caledonian University.
McLean
M
M
MacAulay
L
L
Shaw
A M
AM
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D017536:Carotid Artery, Common / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004983:Ethanolamines / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D010648:Phenylacetates / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013928:Thromboxane A2 / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D010648:Phenylacetates; D011943:Receptors, Adrenergic, beta; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; C057368:BRL 37344; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011433:Propranolol; D007545:Isoproterenol; C102383:talibegron hydrochloride; D019331:NG-Nitroarginine Methyl Ester