This study/review is aimed at assessing the binding constants and consequently the effective role of Angiotensin II (Ang II) on endothelial and cardiac myocytes in the presence and absence of Angiotensin II type 1 receptor (AT₁-R) and Angiotensin II type 2 receptor (AT₂-R) antagonists in perfused healthy Sprague-Dawley rat hearts. A heart perfusion method was used, the inlet via the aortic lumen, and the outlet via the right atrium and the measured concentration of Ang II in the effluent with time is plotted using concurrently a physical model describing a 1:1 ligand-receptor binding stoichiometry at the microvascular endothelium, and after CHAPS-treatment with cardiac myocytes. A first order impulse function allowed the calculation of the forward binding constant (k_n), the reversible constant (k_-n), the dissociation constant (k_d), and the residency time constant (τ) from the curve fittings. The AT₁-R antagonists [Losartan (LO) and Irbesartan (IR)], and the AT₂-R antagonist [PD 123319(PD)] were dissolved in perfusate at 2μg/mL concentrations. Results show that the AT₁-R embedded at endothelial versus myocyte sites did not show identical affinities. The presence of LO compared to IR in perfusate showed increase in binding affinity of Ang II with the AT₂-R at the endothelial as well as at the cardiac myocyte sites. PD effectively reduced the binding affinity of Ang II with the AT₁-R at the endothelial site, however induced better affinity at the cardiac myocyte site. In conclusion, LO and IR showed differences in pharmacodynamics. In addition, the AT₁-R and AT₂-R are differentially located at the endothelial versus the cardiac myocyte sites, and AT₂-R antagonist may preferentially mediate inhibition of cell proliferation and angiogenesis, and consequently induce cardioprotective effects at the coronary endothelial site.