How does the angiotensin II type 1 receptor 'trump' the type 2 receptor in blood pressure control?

Background: A kinetic model for the binding of angiotensin II (Ang II) to AT1 receptors (AT1Rs) in arterioles did suggest a novel mechanism of association rate amplification and facilitated Ang II diffusion in vivo. Aim of study: To examine how this mechanism, acting on AT1R, will affect the stimulation of AT2R. Method: The model distinguishes between the diffusion of plasma Ang II across the endothelium layer (thickness 10(-4) - 5 x 10(-4) cm) into the vascular smooth muscle (VSM) layer (5 x 10(-4) cm), and the diffusion of tissue Ang II from perivascular interstitium (thickness of micromilieu fluid layer at abluminal VSM surface 10(-6) - 10(-5) cm, i.e. 1 to 10 times the glycocalyx). Thus, Ang II concentration [Ang II] is taken to be 0 at the abluminal and adluminal VSM cell surfaces, respectively. Ti Results: Ang II, at 10(-15) - 10(-13) mol/ml (similar to 1-100 pg/ml), is much less likely to react with vascular AT2R than AT1R, though it has similar affinity for the receptor types. With plasma [Ang II] = 10(-15)-10(-13) mol/ml, AT2R occupancy is less than 10% of maximum on endothelium, and virtually 0 on VSM, whereas AT1R occupancy on VSM is virtually 0 at plasma [Ang II] < 10(-14) mol/ml, and between 0 and 30% at plasma [Ang II] = 10(-13) mol/ml. With tissue [Ang II] = 10(-15)-10(-13) mol/m Conclusion: The threshold concentration of Ang II needed for response is much higher for AT2R than for AT1R. Plasma Ang II rather than tissue Ang II is the agonist of AT2R, and the reverse applies to AT1R. Thus, AT2R stimulation may come into play only at unusually high circulating levels of Ang II.