Effect of β /β -adrenoceptor blockade on β -adrenoceptor activity in the rat cremaster muscle artery.

Background And Purpose: 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.

Experimental Approach: 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.

Key Results: 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.

Conclusion And Implications: 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.