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(Circulation. 2002;106:550.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

Norepinephrine Elicits ß₂-Receptor–Mediated Dilation of Isolated Human Coronary Arterioles

Dong Sun, MD, PhD; An Huang, MD, PhD; Seema Mital, MD; Maryanne R. Kichuk, MD; Charles C. Marboe, MD; Linda J. Addonizio, MD; Robert E. Michler, MD; Akos Koller, MD, PhD; Thomas H. Hintze, PhD; Gabor Kaley, PhD

From the Department of Physiology (D.S., A.H., A.K., T.H.H., G.K.), New York Medical College, Valhalla, and the Department of Surgery (S.M., M.R.K., C.C.M., L.J.A., R.E.M.), Division of Cardiothoracic Surgery and the Transplant Service, Columbia University, College of Physicians and Surgeons, New York, NY. Dr Kichuk is now at The Cleveland Clinic, Cleveland, Ohio, and Dr Michler is now at Ohio University Medical Center, Columbus.

Correspondence to Gabor Kaley, PhD, Department of Physiology, New York Medical College, Valhalla, NY 10595. E-mail Gabor_Kaley@ nymc.edu

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 3x10^{- 7} mol/L) elicited concentration-dependent dilations (47±4 µm) that were unaffected by endothelium removal, N-nitro-L-arginine (10^{- 4} mol/L, an NO synthase inhibitor), or practolol (10^-6 mol/L, a ß ₁-receptor blocker). However, administration of propranolol (10^-5 mol/L, a combined ß ₁- and ß₂-blocker) or butoxamine (10^-6 mol/L, a ß ₂-receptor blocker) completely eliminated the NE-induced dilation. Constrictions to NE (2 of 39 vessels) were inhibited by prazosin (10^-6 mol/L, an ₁-receptor blocker). Methoxamine (10^{- 9} to 10^-5 mol/L, an ₁-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 ß₂-receptors on smooth muscle. These findings are important to our understanding of the mechanisms action of NE in the human coronary circulation.

Key Words: norepinephrine • receptors, adrenergic • arteries

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