Increased Expression Of Prorenin Receptor (Prr) In The Nts Of Spontaneously Hypertensive Rats (Shr) May Be A Compensatory Mechanism Of Hypertension

PRR expression is significantly increased in the nucleus of the solitary tract (NTS) of SHR compared to WKY controls. This observation led us to hypothesize that increased NTS PRR expression is linked to hypertension. We test this hypothesis by chronic knockdown or overexpression PRR in the NTS using AAV vector mediated gene transfer. Knockdown of PRR by AAV2‐PRR‐shRNA in SHR resulted in a 22 mmHg increase in mean arterial pressure (MAP) (shRNA: 173±5; Control: 151±6 mm Hg) along with shifting the set point of arterial pressure to a higher level. However, no changes were observed on MAP in WKY rats. Consistent with pressor effects of PRR knockdown, overexpression of PRR in SHR by AAV2‐human‐PRR induced a 19 mmHg decrease in MAP (PRR: 148±7; Control: 167±7 mmHg) compared to control animals. Finally, we measured the effect of increased PRR ligand, prorenin on blood pressure. Bilateral acute NTS injection of human renin (2 pmol/side) produced significant greater decreases in MAP and heart rate (HR) in SHR (ΔMAP: −32±5 mmHg, ΔHR; −40±10 bpm) compared to WKY rats (ΔMAP: −8±4 mmHg; ΔHR: −12±7 bpm). These effects in SHR were attenuated (70%) by prorenin handle region peptide, but were not affected by AT1 or AT2 receptor blockers. This study suggests that increased NTS PRR expression may be a compensatory mechanism of hypertension and that it mediates an anti‐hypertensive effect in an Ang II independent mechanism. ( AHA 11SDG7420029)