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Increased (Pro)renin Receptor Expression in the Hypertensive Human Brain
AdvisorEarley, Yumei Feng
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The renin-angiotensin system (RAS) is one of the important physiologicalpathways controlling blood pressure notably the over-activation of the RAS leads tohypertension. It is well recognized that the central nervous system has its own local RAS,and the majority of its components are known to be expressed in the brain. However, reninlevels in the brain are very low; interestingly, in both normal physiological andpathological 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 IIindependentPRR signaling. Previous studies showed that expression of the PRR isincreased in cardiovascular regulatory nuclei in hypertensive animal models and plays animportant role on BP regulation in the central nervous system. To determine the clinicalsignificance of brain PRR in human hypertension, we investigated whether the PRR isexpressed and regulated in two key cardiovascular regulatory nuclei, the paraventricularnucleus of hypothalamus (PVN) and rostral ventrolateral medulla (RVLM), in postmortembrain samples of normotensive and hypertensive humans. Here, we report that PRR isexpressed in neurons but not in astrocytes of the human PVN and RVLM. We also foundthat PRR is expressed in the catecholaminergic neurons of the RVLM. PRRimmunoreactivity in both the PVN and RVLM were significantly increased in hypertensivesubjects. In addition, PVN-PRR immunoreactivity is positively correlated with systolic BP.Our data provided clinical evidence that the PRR in the PVN and RVLM may be a keymolecular player for the neural regulation of BP in humans.