Physiology, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Br J Pharmacol. 2021 Apr;178(8):1789-1804. doi: 10.1111/bph.15398. Epub 2021 Feb 27.
The physiological role of vascular β -adrenoceptors is not fully understood. Recent evidence suggests cardiac β -adrenoceptors are functionally effective after down-regulation of β /β -adrenoceptors. The functional interaction between the β -adrenoceptor and other β-adrenoceptor subtypes in rat striated muscle arteries was investigated.
Studies were performed in cremaster muscle arteries isolated from male Sprague-Dawley rats. β-adrenoceptor expression was assessed through RT-PCR and immunofluorescence. Functional effects of β -adrenoceptor agonists and antagonists and other β-adrenoceptor ligands were measured using pressure myography.
All three β-adrenoceptor subtypes were present in the endothelium of the cremaster muscle artery. The β -adrenoceptor agonists mirabegron and CL 316,243 had no effect on the diameter of pressurized (70 mmHg) cremaster muscle arterioles with myogenic tone, while the β -adrenoceptor agonist SR 58611A and the nonselective β-adrenoceptor agonist isoprenaline caused concentration-dependent dilation. In the presence of β -adrenoceptor antagonists nadolol (10 μM), atenolol (1 μM) and ICI 118,551 (0.1 μM) both mirabegron and CL 316,243 were effective in causing vasodilation and the potency of SR 58611A was enhanced, while responses to isoprenaline were inhibited. The β -adrenoceptor antagonist L 748,337 (1 μM) inhibited vasodilation caused by β -adrenoceptor agonists (in the presence of β -adrenoceptor blockade), but L 748,337 had no effect on isoprenaline-induced vasodilation.
All three β-adrenoceptor subtypes were present in the endothelium of the rat cremaster muscle artery, but β -adrenoceptor mediated vasodilation was only evident after blockade of β -adrenoceptors. This suggests constitutive β -adrenoceptor activity inhibits β -adrenoceptor function in the endothelium of skeletal muscle resistance arteries.
血管β-肾上腺素能受体的生理作用尚未完全阐明。最近的证据表明，心脏β-肾上腺素能受体在β/β-肾上腺素能受体下调后具有功能性。本研究旨在探讨大鼠横纹肌动脉中β-肾上腺素能受体与其他β-肾上腺素能受体亚型之间的功能相互作用。
本研究在雄性 Sprague-Dawley 大鼠的提睾肌动脉中进行。通过 RT-PCR 和免疫荧光法评估β-肾上腺素能受体的表达。使用压力测微法测量β-肾上腺素能受体激动剂和拮抗剂以及其他β-肾上腺素能配体的功能效应。
三种β-肾上腺素能受体亚型均存在于提睾肌动脉的内皮细胞中。β-肾上腺素能受体激动剂米拉贝隆和 CL 316,243 对有肌源性张力的加压（70mmHg）提睾肌小动脉的直径没有影响，而β-肾上腺素能受体激动剂 SR 58611A 和非选择性β-肾上腺素能受体激动剂异丙肾上腺素则引起浓度依赖性扩张。在β-肾上腺素能受体拮抗剂纳多洛尔（10μM）、阿替洛尔（1μM）和 ICI 118,551（0.1μM）存在的情况下，米拉贝隆和 CL 316,243 均可有效引起血管扩张，并且 SR 58611A 的效力增强，而异丙肾上腺素的反应受到抑制。β-肾上腺素能受体拮抗剂 L 748,337（1μM）抑制β-肾上腺素能受体激动剂引起的血管扩张（在β-肾上腺素能受体阻断的情况下），但 L 748,337 对异丙肾上腺素引起的血管扩张没有影响。
三种β-肾上腺素能受体亚型均存在于大鼠提睾肌动脉的内皮细胞中，但只有在阻断β-肾上腺素能受体后，β-肾上腺素能受体介导的血管扩张才明显。这表明组成型β-肾上腺素能受体活性抑制了骨骼肌阻力动脉内皮细胞中的β-肾上腺素能受体功能。
