{"title":"心得安和L-NAME对大鼠颈动脉β-肾上腺素受体介导的舒张的影响","authors":"A. MacDonald, M. McLean, L. MacAulay, A. M. Shaw","doi":"10.1046/j.1365-2680.1999.00128.x","DOIUrl":null,"url":null,"abstract":"<p> <b>1</b> The properties of β-adrenoceptors mediating vascular relaxation in rat isolated carotid artery were investigated. Ring segments of arteries were preconstricted with the thromboxane A<sub>2</sub> receptor agonist U-46619 and relaxation to β-adrenoceptor agonists determined.</p><p> <b>2</b> 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 μ<span>m</span>) although the shift was less (105 fold; pA<sub>2</sub>, 8.02) than would be expected for an effect of isoprenaline at classical β-adrenoceptors (300–1000 fold; pA<sub>2</sub>, 8.5–9). L-NAME (100 μ<span>m</span>) significantly reduced responses to isoprenaline, lowering the slope of the CRC and reducing the maximum response.</p><p> <b>3</b> The selective β<sub>3</sub>-adrenoceptor agonists, BRL 37344 and ZD2079, also produced concentration-dependent relaxation of the arteries. L-NAME (100 μ<span>m</span>) shifted the BRL 37344 CRC to the right 15 fold with no reduction in the slope or maximum response. L-NAME (100 μ<span>m</span>) had no significant effect on the ZD2079 CRC.</p><p> <b>4</b> In conclusion, relaxation to isoprenaline in rat carotid artery is inhibited by propranolol in a manner suggesting a mixed population of classical (β<sub>1</sub>-/β<sub>2</sub>-) and atypical (β<sub>3</sub>-) adrenoceptors. The presence of β<sub>3</sub>-adrenoceptors was confirmed by the relaxant effects of the selective β<sub>3</sub>-adrenoceptor agonists BRL 37344 and ZD2079. L-NAME attenuated responses to both isoprenaline and the β<sub>3</sub>-adrenoceptor agonist BRL 37344, suggesting a role for endothelial release of nitric oxide in β-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 β-and β<sub>3</sub>-adrenoceptor-mediated effects, with endothelium contributing less to β<sub>3</sub>-adrenoceptor-mediated relaxation.</p>","PeriodicalId":100151,"journal":{"name":"Autonomic and Autacoid Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2008-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-2680.1999.00128.x","citationCount":"38","resultStr":"{\"title\":\"Effects of propranolol and L-NAME on β-adrenoceptor-mediated relaxation in rat carotid artery\",\"authors\":\"A. MacDonald, M. McLean, L. MacAulay, A. M. Shaw\",\"doi\":\"10.1046/j.1365-2680.1999.00128.x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p> <b>1</b> The properties of β-adrenoceptors mediating vascular relaxation in rat isolated carotid artery were investigated. Ring segments of arteries were preconstricted with the thromboxane A<sub>2</sub> receptor agonist U-46619 and relaxation to β-adrenoceptor agonists determined.</p><p> <b>2</b> 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 μ<span>m</span>) although the shift was less (105 fold; pA<sub>2</sub>, 8.02) than would be expected for an effect of isoprenaline at classical β-adrenoceptors (300–1000 fold; pA<sub>2</sub>, 8.5–9). L-NAME (100 μ<span>m</span>) significantly reduced responses to isoprenaline, lowering the slope of the CRC and reducing the maximum response.</p><p> <b>3</b> The selective β<sub>3</sub>-adrenoceptor agonists, BRL 37344 and ZD2079, also produced concentration-dependent relaxation of the arteries. L-NAME (100 μ<span>m</span>) shifted the BRL 37344 CRC to the right 15 fold with no reduction in the slope or maximum response. L-NAME (100 μ<span>m</span>) had no significant effect on the ZD2079 CRC.</p><p> <b>4</b> In conclusion, relaxation to isoprenaline in rat carotid artery is inhibited by propranolol in a manner suggesting a mixed population of classical (β<sub>1</sub>-/β<sub>2</sub>-) and atypical (β<sub>3</sub>-) adrenoceptors. The presence of β<sub>3</sub>-adrenoceptors was confirmed by the relaxant effects of the selective β<sub>3</sub>-adrenoceptor agonists BRL 37344 and ZD2079. L-NAME attenuated responses to both isoprenaline and the β<sub>3</sub>-adrenoceptor agonist BRL 37344, suggesting a role for endothelial release of nitric oxide in β-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 β-and β<sub>3</sub>-adrenoceptor-mediated effects, with endothelium contributing less to β<sub>3</sub>-adrenoceptor-mediated relaxation.</p>\",\"PeriodicalId\":100151,\"journal\":{\"name\":\"Autonomic and Autacoid Pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2008-10-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1046/j.1365-2680.1999.00128.x\",\"citationCount\":\"38\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Autonomic and Autacoid Pharmacology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1046/j.1365-2680.1999.00128.x\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Autonomic and Autacoid Pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1046/j.1365-2680.1999.00128.x","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Effects of propranolol and L-NAME on β-adrenoceptor-mediated relaxation in rat carotid artery
1 The properties of β-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 β-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 μm) although the shift was less (105 fold; pA2, 8.02) than would be expected for an effect of isoprenaline at classical β-adrenoceptors (300–1000 fold; pA2, 8.5–9). L-NAME (100 μm) significantly reduced responses to isoprenaline, lowering the slope of the CRC and reducing the maximum response.
3 The selective β3-adrenoceptor agonists, BRL 37344 and ZD2079, also produced concentration-dependent relaxation of the arteries. L-NAME (100 μm) shifted the BRL 37344 CRC to the right 15 fold with no reduction in the slope or maximum response. L-NAME (100 μm) 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 (β1-/β2-) and atypical (β3-) adrenoceptors. The presence of β3-adrenoceptors was confirmed by the relaxant effects of the selective β3-adrenoceptor agonists BRL 37344 and ZD2079. L-NAME attenuated responses to both isoprenaline and the β3-adrenoceptor agonist BRL 37344, suggesting a role for endothelial release of nitric oxide in β-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 β-and β3-adrenoceptor-mediated effects, with endothelium contributing less to β3-adrenoceptor-mediated relaxation.
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