Angiotensin II type 2 receptor - Mediated vasodilation in human coronary microarteries

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 mum) 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 Emax to 97 +/- 14% (P < 0.05). The increase in Emax was larger in older donors ( correlation Delta E-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.