Effect of Beta(1)/Beta(2)-Adrenoceptor Inhibition on Beta(3)-Adrenoceptor Activity in the Rat Cremaster Muscle Artery

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British Journal of Pharmacology





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Background and Purpose The physiological role of vascular beta(3)-adrenoceptors is not fully understood. Recent evidence suggests cardiac beta(3)-adrenoceptors are functionally effective after down-regulation of beta(1)/beta(2)-adrenoceptors. The functional interaction between the beta(3)-adrenoceptor and other beta-adrenoceptor subtypes in rat striated muscle arteries was investigated. Experimental Approach Studies were performed in cremaster muscle arteries isolated from male Sprague-Dawley rats. beta-adrenoceptor expression was assessed through RT-PCR and immunofluorescence. Functional effects of beta(3)-adrenoceptor agonists and antagonists and other beta-adrenoceptor ligands were measured using pressure myography. Key Results All three beta-adrenoceptor subtypes were present in the endothelium of the cremaster muscle artery. The beta(3)-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 beta(3)-adrenoceptor agonist SR 58611A and the nonselective beta-adrenoceptor agonist isoprenaline caused concentration-dependent dilation. In the presence of beta(1/2)-adrenoceptor antagonists nadolol (10 mu M), atenolol (1 mu M) and ICI 118,551 (0.1 mu M) 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 beta(3)-adrenoceptor antagonist L 748,337 (1 mu M) inhibited vasodilation caused by beta(3)-adrenoceptor agonists (in the presence of beta(1/2)-adrenoceptor blockade), but L 748,337 had no effect on isoprenaline-induced vasodilation. Conclusion and Implications All three beta-adrenoceptor subtypes were present in the endothelium of the rat cremaster muscle artery, but beta(3)-adrenoceptor mediated vasodilation was only evident after blockade of beta(1/2)-adrenoceptors. This suggests constitutive beta(1/2)-adrenoceptor activity inhibits beta(3)-adrenoceptor function in the endothelium of skeletal muscle resistance arteries.


Beta-adrenoceptor; Artery; Endothelium; Nitric oxide


Life Sciences | Pharmacology | Pharmacology, Toxicology and Environmental Health



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