Key result
Mas receptor agonists lower blood pressure and promote vasorelaxation in preclinical hypertension models.
Why the study?
The pathophysiology of essential hypertension needs clarification, and the clinical potential of targeting the vasoprotective Mas receptor remains unclear due to complex RAAS signaling pathways.
Targeting the protective ACE2/Ang-(1-7)/MasR axis offers a promising novel pharmacological strategy for treating essential hypertension beyond classical RAAS blockade.
May support Mas receptor agonists for hypertension; leaves open clinical translation from preclinical models.
The renin–angiotensin–aldosterone system (RAAS) has been studied extensively, and with the inclusion of novel components, it has become evident that the system is much more complex than originally anticipated. According to current knowledge, there are two main axes of the RAAS, which counteract each other in terms of vascular control: The classical vasoconstrictive axis, renin/angiotensin-converting enzyme/angiotensin II/angiotensin II receptor type 1 (AT1R), and the opposing vasorelaxant axis, angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas receptor (MasR). An abnormal activity within the system constitutes a hallmark in hypertension, which is a global health problem that predisposes cardiovascular and renal morbidities. In particular, essential hypertension predominates in the hypertensive population of more than 1.3 billion humans worldwide, and yet, the pathophysiology behind this multifactorial condition needs clarification. While commonly applied pharmacological strategies target the classical axis of the RAAS, discovery of the vasoprotective effects of the opposing, vasorelaxant axis has presented encouraging experimental evidence for a new potential direction in RAAS-targeted therapy based on the G protein-coupled MasR. In addition, the endogenous MasR agonist angiotensin-(1-7), peptide analogues, and related molecules have become the subject of recent studies within this field. Nevertheless, the clinical potential of MasR remains unclear due to indications of physiological-biased activities of the RAAS and interacting signaling pathways.
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Povlsen et al. (2020) conducted a review in Essential Hypertension. Mas receptor agonists and Angiotensin-(1-7) analogues was evaluated. Mas receptor agonists and Ang-(1-7) analogues demonstrated vasorelaxant and antihypertensive effects in preclinical models, offering a potential novel therapeutic direction for essential hypertension.
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