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

Autonomic and Autacoid Pharmacology Pub Date : 2008-10-09 DOI:10.1046/j.1365-2680.1999.00128.x

A. MacDonald, M. McLean, L. MacAulay, A. M. Shaw

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引用次数: 38

Abstract

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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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

研究β-肾上腺素能受体介导离体大鼠颈动脉血管舒张的特性。用血栓素A2受体激动剂U-46619预缩动脉环段，并测定β-肾上腺素受体激动剂的松弛。异丙肾上腺素对u -44619收缩的动脉产生浓度依赖性松弛。心得安(1 μm)对异丙肾上腺素的浓度响应曲线(CRC)右移较小(105倍;pA2, 8.02)比异丙肾上腺素对经典β-肾上腺素受体的影响(300-1000倍;章,8.5 9)。L-NAME (100 μm)显著降低了对异丙肾上腺素的响应，降低了CRC的斜率，降低了最大响应。选择性β3-肾上腺素能受体激动剂BRL 37344和ZD2079也能产生浓度依赖性的动脉舒张。L-NAME (100 μm)将BRL 37344 CRC右移15倍，斜率和最大响应均未降低。L-NAME (100 μm)对ZD2079 CRC无显著影响。综上所述，心得安可以抑制大鼠颈动脉对异丙肾上腺素的松弛，其方式表明经典(β1-/β2-)和非典型(β3-)肾上腺素受体的混合种群。选择性β3-肾上腺素受体激动剂BRL 37344和ZD2079的松弛作用证实了β3-肾上腺素受体的存在。L-NAME可减弱对异丙肾上腺素和β3-肾上腺素受体激动剂BRL 37344的反应，提示一氧化氮的内皮释放在β-肾上腺素受体介导的松弛中起作用。然而，BRL 37344的松弛作用被L-NAME减弱的程度小于异丙肾上腺素。此外，L-NAME对ZD2079诱导的松弛无影响。这些结果表明，内皮对经典β和β3-肾上腺素受体介导的作用可能有不同的贡献，内皮对β3-肾上腺素受体介导的松弛作用的贡献较小。

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