Renin Gene Transfer Restores Angiogenesis and Vascular Endothelial Growth Factor Expression in Dahl S Rats

Abstract

In a previous study, we demonstrated that Dahl S rats (SS group) have low plasma renin activity, whereas transfer of a region of chromosome 13 containing the renin gene from Dahl R onto a congenic strain of Dahl SS/Jr/Hsd/MCW rats (S/ren RR group) restores renin secretory responses. In the present study, we compared the angiogenic responses to electrical stimulation in the SS and S/ren RR groups to explore the hypotheses that the renin-angiotensin system is involved in vascular endothelial growth factor (VEGF) expression and angiogenesis in skeletal muscle. Congenic SS and S/ren RR rats fed a 0.4% or 4% salt diet were surgically prepared by chronic implantation of an electrical stimulator. Another group of S/ren RR rats was treated with lisinopril 2 days before the surgery and throughout the stimulation protocol. The right tibialis anterior (TA) and extensor digitorum longus (EDL) were stimulated for 8 hours per day for 7 days. The contralateral muscles served as controls. Western blot analysis was performed to identify VEGF protein expression in these muscles. Electrical stimulation produced no change in vessel density of the SS group fed a 0.4% salt diet (change 5.50% and 8.14% for EDL and TA, respectively). Transfer of a region containing the renin gene restored the angiogenic response (change 16% and 30% for EDL and TA, respectively) despite a significantly higher blood pressure. Blockade of the renin-angiotensin system by lisinopril or high salt restored the responses observed in the SS group fed a low salt diet. In addition, increases in VEGF expression to electrical stimulation were observed only in the S/ren RR group fed a low salt diet. These results suggest that renin gene transfer restores angiogenesis and VEGF expression in the skeletal muscle of Dahl S rats.