Published online before print April 26, 2004, doi: 10.1161/01.CIR.0000128696.12245.57
(Circulation. 2004;109:2296-2301.)
© 2004 American Heart Association, Inc.
Clinical Investigation and Reports |
Angiotensin II Type 2 Receptor–Mediated Vasodilation in Human Coronary Microarteries
From the Department of Pharmacology (W.W.B., I.M.G., P.R.S., A.H.J.D.) and the Department of Thoracic Surgery and Heart Valve Bank (J.P.v.K.), Lausanne), Erasmus MC, Rotterdam, the Netherlands; and the University Institute of Pathology (C.C.B., L.J.-J.), Lausanne, Switzerland.
Correspondence to Prof Dr A.H.J. Danser, Department of Pharmacology, Room EE1418b, Erasmus MC, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. E-mail a.danser{at}erasmusmc.nl
Received August 13, 2002; revision received December 2, 2003; accepted February 18, 2004.
Background— Angiotensin (Ang) II type 2 (AT2) receptor stimulation results in coronary vasodilation in the rat heart. In contrast, AT2 receptor–mediated vasodilation could not be observed in large human coronary arteries. We studied Ang II–induced vasodilation of human coronary microarteries (HCMAs).
Methods and Results— HCMAs (diameter, 160 to 500 µm) were obtained from 49 heart valve donors (age, 3 to 65 years). Ang II constricted HCMAs, mounted in Mulvany myographs, in a concentration-dependent manner (pEC50, 8.6±0.2; maximal effect [Emax], 79±13% of the contraction to 100 mmol/L K+). The Ang II type 1 receptor antagonist irbesartan prevented this vasoconstriction, whereas the AT2 receptor antagonist PD123319 increased Emax to 97±14% (P<0.05). The increase in Emax was larger in older donors (correlation 
Emax versus age, r=0.47, P<0.05). The PD123319-induced potentiation was not observed in the presence of the NO synthase inhibitor L-NAME, the bradykinin type 2 (B2) receptor antagonist Hoe140, or after removal of the endothelium. Ang II relaxed U46619-preconstricted HCMAs in the presence of irbesartan by maximally 49±16%, and PD123319 prevented this relaxation. Finally, radioligand binding studies and reverse transcription–polymerase chain reaction confirmed the expression of AT2 receptors in HCMAs.
Conclusions— AT2 receptor–mediated vasodilation in the human heart appears to be limited to coronary microarteries and is mediated by B2 receptors and NO. Most likely, AT2 receptors are located on endothelial cells, and their contribution increases with age.
Key Words: angiotensin • bradykinin • microcirculation • nitric oxide • vasodilation
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