β-肾上腺素受体参与选择性腺苷 A2A 和 A2B 受体激动剂诱导的心血管反应,Pharmacology Research & Perspectives

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β-肾上腺素受体参与选择性腺苷 A2A 和 A2B 受体激动剂诱导的心血管反应
Pharmacology Research & Perspectives ( IF 2.9 ) Pub Date : 2022-05-29 , DOI: 10.1002/prp2.975
Edward S Wragg _{1,

2} , Patrizia Pannucci _{1,

2} , Stephen J Hill _{1,

2} , Jeanette Woolard _{1,

2} , Samantha L Cooper _{1,

2}

Affiliation

A _2A和A _2B腺苷受体对血管张力产生区域选择性调节，并对平均动脉压(MAP) 产生不同的影响，同时诱发心动过速。已表明由 A _2A或 A _2B受体刺激引起的心动过速是由交感神经活动的反射性增加介导的。_{在这里，我们研究了 β 1} - 和 β _{2 -肾上腺素能受体在介导对选择性 A}_2A和 A _2B的不同心血管反应中的作用受体刺激。通过脉冲多普勒血流计测量有意识的雄性 Sprague-Dawley 大鼠 (350–450 g) 的血流动力学变量。A _2A选择性激动剂 CGS 21680（0.1、0.3、1.0 µg.kg ⁻¹ .min ⁻¹）或 A _2B选择性激动剂 BAY 60–6583（4.0， 13.3, 40.0 µg.kg ^-1 .min ^-1 ) 在没有或在用非选择性 β-拮抗剂普萘洛尔 (1.0 mg.kg ^-1 )、选择性 β _{1 -}拮抗剂 CGP 20712A (200 µg .kg ^-1 )，或选择性β ₂ -拮抗剂ICI 118,551 (2.0 mg.kg ^-1) 进行了调查（也给予了维持剂量）。CGP 20712A 和心得安显着降低了对 CGS 21680 的心动过速反应，而对 MAP 的影响没有变化。ICI 118,551 增加了 BAY 60–6583 介导的肾脏和肠系膜流量，但不影响心率反应。CGP 20712A 减弱了 BAY 60–6583 诱导的心动过速。_{这些数据暗示通过心脏 β 1} -肾上腺素能受体直接刺激交感神经活动作为 A _2A - 和 A _{2B -}诱发的心动过速的机制。_{然而，A 2B}激动剂对血管传导的区域选择性作用与交感神经活动无关，可用于治疗急性肾损伤和肠系膜缺血。

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Involvement of β-adrenoceptors in the cardiovascular responses induced by selective adenosine A2A and A2B receptor agonists

A_2A and A_2B adenosine receptors produce regionally selective regulation of vascular tone and elicit differing effects on mean arterial pressure (MAP), whilst inducing tachycardia. The tachycardia induced by the stimulation of A_2A or A_2B receptors has been suggested to be mediated by a reflex increase in sympathetic activity. Here, we have investigated the role of β₁- and β₂-adrenoceptors in mediating the different cardiovascular responses to selective A_2A and A_2B receptor stimulation. Hemodynamic variables were measured in conscious male Sprague-Dawley rats (350–450 g) via pulsed Doppler flowmetry. The effect of intravenous infusion (3 min per dose) of the A_2A-selective agonist CGS 21680 (0.1, 0.3, 1.0 µg.kg⁻¹.min⁻¹) or the A_2B-selective agonist BAY 60–6583 (4.0, 13.3, 40.0 µg.kg⁻¹.min⁻¹) in the absence or following pre-treatment with the non-selective β-antagonist propranolol (1.0 mg.kg⁻¹), the selective β₁-antagonist CGP 20712A (200 µg.kg⁻¹), or the selective β₂-antagonist ICI 118,551 (2.0 mg.kg⁻¹) was investigated (maintenance doses also administered). CGP 20712A and propranolol significantly reduced the tachycardic response to CGS 21680, with no change in the effect on MAP. ICI 118,551 increased BAY 60–6583-mediated renal and mesenteric flows, but did not affect the heart rate response. CGP 20712A attenuated the BAY 60–6583-induced tachycardia. These data imply a direct stimulation of the sympathetic activity via cardiac β₁-adrenoceptors as a mechanism for the A_2A- and A_2B-induced tachycardia. However, the regionally selective effects of A_2B agonists on vascular conductance were independent of sympathetic activity and may be exploitable for the treatment of acute kidney injury and mesenteric ischemia.

更新日期：2022-05-31

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