Angiotensin II Type 2 Receptor–Mediated Vasodilation in Human Coronary Microarteries

Abstract

Background— Angiotensin (Ang) II type 2 (AT 2 ) receptor stimulation results in coronary vasodilation in the rat heart. In contrast, AT 2 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 (pEC 50 , 8.6±0.2; maximal effect [E max ], 79±13% of the contraction to 100 mmol/L K + ). The Ang II type 1 receptor antagonist irbesartan prevented this vasoconstriction, whereas the AT 2 receptor antagonist PD123319 increased E max to 97±14% ( P <0.05). The increase in E max was larger in older donors (correlation ΔE max 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 (B 2 ) 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 AT 2 receptors in HCMAs. Conclusions— AT 2 receptor–mediated vasodilation in the human heart appears to be limited to coronary microarteries and is mediated by B 2 receptors and NO. Most likely, AT 2 receptors are located on endothelial cells, and their contribution increases with age.