The renin-angiotensin system and cardiovascular autonomic control in aging

Abstract

Aging is the greatest independent risk factor for developing hypertension and cardiovascular-related diseases including systolic hypertension, vascular disease, ischemic events, arrhythmias, and heart failure. Age-related cardiovascular risk is associated with dysfunction of peripheral organ systems, such as the heart and vasculature, as well as an imbalance in the autonomic nervous system characterized by increased sympathetic and decreased parasympathetic neurotransmission. Given the increasing prevalence of aged individuals worldwide, it is critical to better understand mechanisms contributing to impaired cardiovascular autonomic control in this population. In this regard, the renin-angiotensin system has emerged as an important hormonal modulator of cardiovascular function in aging, in part through modulation of autonomic pathways controlling sympathetic and parasympathetic outflow to cardiovascular end organs. This review will summarize the role of the RAS in cardiovascular autonomic control during aging, with a focus on current knowledge of angiotensin II versus angiotensin-(1-7) pathways in both rodent models and humans, pharmacological treatment strategies targeting the renin-angiotensin system, and unanswered questions for future research.

Keywords: Angiotensin; Blood pressure; Parasympathetic; Sympathetic.

Figure 1.. Overview of Cardiovascular and Autonomic Changes in Aging.

Healthy aging is associated with several changes to the cardiovascular system that predispose this population to developing cardiovascular disease. This review will focus on autonomic nervous system mechanisms (bolded), such as reduced baroreceptor sensitivity and increased sympathetic activity, that occur with aging. While not a focus, additional non-autonomic mechanisms occur during aging that impact cardiovascular control such as structural changes to the heart and blood vessels including cardiac fibrosis, left ventricular hypertrophy, endothelial damage, and atherosclerosis. All these changes can manifest clinically as isolated systolic hypertension and arrhythmias in aged individuals.

Figure 2.. Renin-Angiotensin and Autonomic Interactions in Aging for Cardiovascular Control.

During aging, angiotensin II, angiotensin converting enzyme (ACE), and angiotensin type 1 receptor (AT1R) pathways are increased while angiotensin-(1–7), angiotensin converting enzyme 2 (ACE2), and mas receptor (MasR) are decreased. This imbalance in the renin-angiotensin system contributes to impaired measures of parasympathetic tone, such as baroreflex sensitivity (BRS) and heart rate variability (HRV). This reduced parasympathetic tone allows for unrestrained sympathetic activation, which can desensitize adrenergic receptors in the kidney, heart, and vasculature; these end organs are less responsive to sympathetic stimulation in aging.