Effects of the Prdx2 depletion on blood pressure and life span in spontaneously hypertensive rats.

Oxidative stress is involved in the pathogenesis of hypertension and hypertensive organ damage. Our previous study suggested that stroke-prone spontaneously hypertensive rats (SHRSP) exhibited greater oxidative stress than SHR and that the stroke incidence was significantly greater in SHRSP than SHR. Therefore, we hypothesized that oxidative stress was responsible for the stroke susceptibility in SHRSP. The present study constructed Prdx2 (a gene coding an antioxidative enzyme)-knockout (KO) SHR to examine whether Prdx2 knockout would make SHR more vulnerable to hypertensive organ damage, including stroke. Prdx2-KO SHR were created using CRISPR/CAS9 for genome editing. Eight-week-old male SHR and Prdx2-KO SHR were fed 1% NaCl for 2 months to induce blood pressure (BP) changes and stroke occurrence. The baseline BP was significantly greater in KO SHR, and this difference disappeared after salt loading. The life span of KO SHR was significantly reduced compared to that of SHR despite no differences in BP under salt-loading. However, no stroke was observed in KO SHR. The severity of hypertensive renal and cardiac injuries did not differ significantly between the two strains, but oxidative stress, evaluated using urinary isoprostane excretion and DHE staining, was greater in KO SHR. These results indicated that the Prdx2-depletion caused a shorter life span and modest BP increase in SHR via increased oxidative stress. The pathophysiological roles of oxidative stress in this model should be clarified in future studies.