Norepinephrine elicits β₂-receptor-mediated dilation of isolated human coronary arterioles

Background - The exact role of adrenoceptors in norepinephrine (NE)-mediated regulation of the human coronary circulation has yet to be elucidated. Thus, the goals of this study were to characterize the adrenoceptors involved in the responses to NE in isolated human coronary arterioles and small arteries. Methods and Results - Arterioles (n=39) and small arteries from the left ventricle of explanted human hearts were isolated and cannulated. Vessels from the hearts of 21 patients were studied: 15 males and 6 females, aged 0.5 to 63 years. Nineteen patients were considered to be New York Heart Association class 4. All hearts exhibited hypertrophy (190±20%). The passive diameter of arterioles was 167±8 μm (range 97 to 323 μm). NE (10^-7 to 3×10^-7 mol/L) elicited concentration-dependent dilations (47±4 μm) that were unaffected by endothelium removal, N^ω-nitro-L-arginine (10^-4 mol/L, an NO synthase inhibitor), or practolol (10^-6 mol/L, a β₁-receptor blocker). However, administration of propranolol (10^-5 mol/L, a combined β₁- and β₂-blocker) or butoxamine (10^-6 mol/L, a β₂-receptor blocker) completely eliminated the NE-induced dilation. Constrictions to NE (2 of 39 vessels) were inhibited by prazosin (10^-6 mol/L, an α₁-receptor blocker). Methoxamine (10^-9 to 10^-5 mol/L, an α₁-agonist) had no effect, whereas U44619, a thromboxane mimetic, elicited dose-dependent constriction of vessels. Conclusions - Our data indicate that isolated human coronary arterioles and small arteries dilate to NE via β₂-receptors on smooth muscle. These findings are important to our understanding of the mechanisms action of NE in the human coronary circulation.