Interactions between AT1, AT2 and B2 receptors in the response to Ang II in the aorta of SHR rats

Introduction The study of the receptors of the renin-angiotensin and kinin-kallikrein systems and their interactions has enhanced our understanding of hypertension physiology and contributed to the development of improved pharmacological treatments (McCarthy et al. 2025). Objective This work aimed to investigate the functional interactions among AT1, AT2, and B2 receptors specifically the effects of agonist-agonist, agonist-antagonist, and antagonist-antagonist combinations on vasocontractile response to Ang II. Methods Concentration-response curves to Ang II were performed in WKY and SHR rat aortic rings in the presence of bradykinin (BK), valsartan, CGP42112A, HOE140, and their combinations. NO levels were indirectly determinated by the Griess reaction in aortic rings. Results Ang II induced a stronger contractile response in SHR compared with WKY. AT1R antagonism and AT2R receptor stimulation significantly reduced vasoconstriction and increased NO levels. BK also attenuated the contractile response without increasing NO levels. In contrast, blockade of B2R or AT2R did not reduce maximal contraction. Combined treatments involving valsartan or CGP42112A decreased Ang II reactivity. Conclusion Activation of AT2R and B2R counteracts Ang II–induced vasoconstriction through NO-dependent and NO-independent mechanisms. Receptor heterodimerization appears to contribute to these modulatory effects.