Abstract
Overactivation of the renin-angiotensin system (RAS) – a central physiological pathway involved in controlling blood pressure (BP) – leads to hypertension. It is now well-recognized that the central nervous system (CNS) has its own local RAS, and the majority of its components are known to be expressed in the brain. In physiological and pathological states, the (pro)renin receptor (PRR), a novel component of the brain RAS, plays a key role in the formation of angiotensin II (Ang II) and also mediates Ang II-independent PRR signaling. A recent study reported that neuronal PRR activation is a novel mechanism for cardiovascular and metabolic regulation in obesity and diabetes. Expression of the PRR is increased in cardiovascular regulatory nuclei in hypertensive (HTN) animal models and plays an important role in BP regulation in the CNS. To determine the clinical significance of the brain PRR in human hypertension, we investigated whether the PRR is expressed and regulated in the paraventricular nucleus of the hypothalamus (PVN) and rostral ventrolateral medulla (RVLM) – two key cardiovascular regulatory nuclei – in postmortem brain samples of normotensive (NTN) and HTN humans. Here, we report that the PRR is expressed in neurons, but not astrocytes, of the human PVN and RVLM. Notably, PRR immunoreactivity was significantly increased in both the PVN and RVLM of HTN subjects. In addition, PVN-PRR immunoreactivity was positively correlated with systolic BP (sBP) and showed a tendency toward correlation with age but not body mass index (BMI). Collectively, our data provide clinical evidence that the PRR in the PVN and RVLM may be a key molecular player in the neural regulation of BP and cardiovascular and metabolic function in humans.
Highlights
Recent studies have reported that ~46% of United States adults of 20 years of age or older suffer from hypertension (Muntner et al, 2018)
All HTN subjects were clinically diagnosed as HTN with a history of taking anti-HTN medication, and all NTN subjects had a record of normal Blood pressure (BP) with no history of diagnosed hypertension
HTN subjects from whom paraventricular nucleus of the hypothalamus (PVN) samples were acquired had higher systolic BP (sBP) (p = 0.001) and an increased heart rate (HR; p = 0.047) compared with NTN subjects
Summary
Recent studies have reported that ~46% of United States adults of 20 years of age or older suffer from hypertension (Muntner et al, 2018). In addition to the circulatory RAS, various tissues throughout the body, including the brain, kidney, heart, blood vessels, lungs, adipose tissue, adrenal gland, pancreas, liver, placenta, muscle, and the eye, possess all RAS components (Nguyen et al, 2002; Paul et al, 2006; RibeiroOliveira et al, 2008). Notable in this context, overactivation of the brain RAS plays a major role in neurohumoral and autonomic dysregulation, an important mechanism leading to cardiovascular and metabolic disorders, including hypertension (Basting and Lazartigues, 2017; Nakagawa et al, 2020)
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