Increased Expression of the (Pro)renin Receptor in the Subfornical Organ of Hypertensive Humans

We previous reported that (pro)renin receptor (PRR) is functional important in the subfornical organ (SFO) of the brain, a key brain circumventricular organ that is involved in BP regulation and body fluid homeostasis. The SFO PRR mediates Ang II formation and is critical for hypertension development and body fluid homeostasis in hypertension animal models. However, it is not known whether PRR expression level is altered in hypertensive humans and what is the cellular distribution. We have collected human subfornical organ (SFO) tissues post mortem, of which 14 are clinically diagnosed hypertensive and 7 are diagnosed normotensive. Systolic (SBP) and diastolic (DBP) blood pressure, age, body weight, and medications used information was collected. SFO tissues were fixed in 10% formaldehyde and processed for paraffin embedding and sectioning. The age and body weight patterns are similar between the normotensive and hypertensive subjects. Regardless of anti‐hypertension medications, the SBP was significantly higher in clinical diagnosed hypertensive (142.4 ± 4.2 mmHg) compared with the normotensive (118.1 ± 7.7, P =0.007) subjects. There is no difference in DBP between these two groups (74.1±5. VS. 79.29±3.5). SFO sections were used for immunofluorescence double labeling of human PRR with neuronal marker (anti–human neuronal protein HuC/HuD), astrocyte marker (glial fibrillary acidic protein, GFAP), or microglia marker (ionized calcium‐ binding adaptor molecule 1, Iba1). We found that the human PRR is co‐localized only with the HuC/HuD but not GFAP or Iba1 suggests that PRR is majorly expressed in the neurons of human SFO. To examine whether there is alteration of PRR expression in the hypertensive humans, we performed immunohistochemistry labeling of PRR in these tissues. The PRR immuno‐reactivity was significantly higher in the hypertensive subjects (145.3 ± 1.4 Arbitrary Units, AU) compared with the normotensive subjects (135.5 ±1.2 AU, P =0.0002). In addition, there is significant positive correlation between the PRR expression levels and the SBP (Pearson r=0.55, R 2 =0.308, P =0.018) among all normotensive and hypertensive subjects. The data suggests that PRR expression level is elevated in hypertension subjects and there is positive correlation of PRR expression level with systolic BP. We conclude that PRR in the SFO may play important role in the body fluid homeostasis and hypertension development in humans. Support or Funding Information NIH/NHLBI (1R01HL122770) TO YUMEI FENG; NIH/NIGMS (P20GM103440) TO SILVANA G. COOPER