Post-junctional α-adrenoceptors and basal limb vascular tone in healthy men

Abstract

Previous studies have demonstrated that post-junctional α1- and α2-adrenoceptors mediate vasoconstriction in the human forearm. However, the relative contributions of the α-adrenoceptor subtypes to basal limb vascular tone are unknown. In healthy young men, forearm blood flow (FBF; venous occlusion plethysmography) responses to brachial artery administration of prazosin (an α1-adrenoceptor antagonist), yohimbine (an α2-adrenoceptor antagonist) and phentolamine (a Non-selective α-adrenoceptor antagonist) were determined after local β-adrenoceptor blockade with propranolol. In 10 subjects, prazosin increased FBF from 2.4 ± 0.3 to 5.8 ± 1.0 ml (100 ml)-1' min-1 (∼140 %; P < 0.001 vs. baseline). Subsequently, phentolamine further increased FBF to 11.7 ± 1.6 ml (100 ml)-1 min-1 (∼385 %; P < 0.001 vs. baseline). Thus, the average calculated increase in FBF due to removal Of α2-vasoconstrictor tone was greater than that due to removal of α1-tone (5.9 ± 0.8 vs. 3.4 ± 0.8 ml (100 ml)-1 min-1; P < 0.01) and represented ∼63 % of basal sympathetic tone. Complete α1-adrenoceptor blockade was confirmed by a minimal reduction in FBF in response to phenylephrine after prazosin (46 ± 3 vs. 6 ± 4 %; before vs. after blockade) and in a separate group of four subjects, increasing the dose of prazosin threefold did not evoke further forearm vasodilatation. Additionally, the reduction in FBF in response to tryamine (evokes endogenous noradrenaline release) was abolished after phentolamine (40 ± 3 vs. 2 ± 1 %; before vs. after blockade), documenting complete pharmacological sympathectomy. In another group of seven subjects, administering yohimbine prior to phentolamine resulted in similar findings. These observations indicate that vasoconstricting post-junctional α2-adrenoceptors contribute more to basal vascular tone than α1-adrenoceptors in the forearms of young healthy men. The potential physiological and pathophysiological implications of these findings are discussed.