Renal Denervation in the Acute Phase of Ischemic Stroke Provides Brain Protection in Hypertensive Rats

Abstract

Background and Purpose— Renal denervation (RD) may protect against cardiovascular diseases regardless of blood pressure (BP)–lowering effect. We hypothesized that RD can improve the outcome of acute ischemic stroke (AIS) in hypertensive rats. Methods— An AIS model of spontaneously hypertensive stroke-prone rats (SHRSPs) was prepared by 90-minute middle cerebral artery occlusion followed by reperfusion. At 30 minutes poststroke, the SHRSPs were subjected to (1) sham operation or (2) RD to determine the beneficial effects of RD posttreatment. In addition, we evaluated the neuroprotective effects of RD posttreatment in Wistar Kyoto rats and RD pretreatment in SHRSPs with AIS. Results— RD significantly ameliorated neurological deficit and infarct volume at 1 and 7 days after middle cerebral artery occlusion. RD immediately and continuously normalized elevated BP during 24 hours. This normalization of BP by RD was associated with the reduction of cerebral blood flow during both middle cerebral artery occlusion and reperfusion periods. Thus, RD-induced BP normalization seems to ameliorate cerebrovascular overperfusion in SHRSPs with AIS. On the contrary, RD did not affect cerebral vascular resistance or cerebral vasoreactivity and did not increase Akt and endothelial NO synthase phosphorylation, thereby indicating no apparent change of cerebrovascular function. RD significantly attenuated cerebral oxidative stress as estimated by dihydroethidium staining and gp91 phox expression. The beneficial effects were not seen in Wistar Kyoto rats, whereas RD pretreatment improved neurological function in SHRSPs. Conclusions— RD posttreatment improved outcome in the hypertensive AIS rat model. Therefore, we suggest that BP normalization by RD may be a promising therapeutic strategy for AIS.