Protective Role of the AT1 Receptor in the Heart: A Biosensor of Stress

The renin angiotensin systemRenin angiotensin system plays an important role in blood pressure regulation and its primary component angiotensin IIAngiotensin II has been implicated in adverse cardiac remodelingCardiac remodeling in response to hypertensionHypertension. However, questions remain as to whether these actions of angiotensin IIAngiotensin II are mediated directly at the level of the heart via its principal receptor, AT1R. A more nuanced reading of the literature suggests that AT1R acts in concert with other signaling events, such as inflammation and tyrosine kinase receptor transactivation, to induce cardiac hypertrophyCardiac hypertrophy under chronic conditions. Here we highlight evidence for an underappreciated, but equally relevant role for AT1R in coupling to a protective program in cardiomyocytesCardiomyocytes with hypertensionHypertension. Recent advances in identifying receptor conformations specific to membrane stretch using nanobodies will allow for further study on AT1R coupling to protective signaling. These studies will expand our understanding of AT1R regulation and possibly lay the groundwork for pharmaceutical exploitation. In any event, AT1R is likely to reveal additional surprises with relevance to cardiac function and remodeling under stress conditions.