Vernail Victoria L, Lucas Lillia, Miller Amanda J, Arnold Amy C
Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Department of Physical Therapy, Lebanon Valley College, Annville, PA 17003, USA.
Int J Mol Sci. 2024 Dec 12;25(24):13320. doi: 10.3390/ijms252413320.
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.
高血压是心血管疾病发生的主要独立危险因素，而心血管疾病是全球首要死因。重要的是，高血压患病率与肥胖呈正相关，由于该人群缺乏现行指南，以及现有抗高血压治疗药物疗效有限且存在不良脱靶效应，与肥胖相关的高血压难以治疗。这凸显了更好地理解高血压与肥胖之间联系的机制以开发最佳治疗方法的必要性。在这方面，肾素 - 血管紧张素系统在高血压和肥胖中均失调，是主要的治疗靶点。虽然研究和治疗通常集中在肾素 - 血管紧张素系统有害的血管紧张素II轴上，但新出现的证据表明，靶向保护性的血管紧张素 -（1 - 7）轴也能改善肥胖高血压动物模型的心血管和代谢功能。虽然其中涉及的精确机制仍在研究中，但除了外周作用外，有证据支持中枢神经系统在血管紧张素 -（1 - 7）有益的心脏代谢作用中发挥作用。本综述将重点介绍探索血管紧张素 -（1 - 7）心血管和代谢调节作用的新兴转化研究，重点是其在脑干和下丘脑等脑区的中枢作用。更好地理解血管紧张素 -（1 - 7）调节心血管和代谢功能所涉及的中枢机制，可能有助于深入了解将这种激素作为肥胖相关高血压新治疗方法的潜力。
