Angiotensin-(1-7) and Central Control of Cardiometabolic Outcomes: Implications for Obesity Hypertension

Hypertension is a leading independent risk factor for the development of cardiovascular disease, the leading cause of death globally. Importantly, the prevalence of hypertension is positively correlated with obesity, with obesity-related hypertension being difficult to treat due to a lack of current guidelines in this population as well as limited efficacy and adverse off-target effects of currently available antihypertensive therapeutics. This highlights the need to better understand the mechanisms linking hypertension with obesity to develop optimal therapeutic approaches. In this regard, the renin-angiotensin system, which is dysregulated in both hypertension and obesity, is a prime therapeutic target. While research and therapies have typically focused on the deleterious angiotensin II axis of the renin-angiotensin system, emerging evidence shows that targeting the protective angiotensin-(1-7) axis also improves cardiovascular and metabolic functions in animal models of obesity hypertension. While the precise mechanisms involved remain under investigation, in addition to peripheral actions, evidence exists to support a role for the central nervous system in the beneficial cardiometabolic effects of angiotensin-(1-7). This review will highlight emerging translational studies exploring the cardiovascular and metabolic regulatory actions of angiotensin-(1-7), with an emphasis on its central actions in brain regions including the brainstem and hypothalamus. An improved understanding of the central mechanisms engaged by angiotensin-(1-7) to regulate cardiovascular and metabolic functions may provide insight into the potential of targeting this hormone as a novel therapeutic approach for obesity-related hypertension.