Renin gene transfer restores angiogenesis and vascular endothelial growth factor expression in Dahl S rats

In a previous study, we demonstrated that Dahl 8 rats (SS group) have low p lasma renin activity, whereas transfer of a region of chromosome 13 contain ing 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 th e SS and S/ren(RR) groups to explore the hypotheses that the renin-angioten sin system is involved in vascular endothelial growth factor (VEGF) express ion 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 protoc ol. The right tibialis anterior (TA) and extensor digitorum longus (EDL) we re stimulated for 8 hours per day for 7 days. The contralateral muscles ser ved as controls. Western blot analysis was performed to identify VEGF prote in expression in these muscles. Electrical stimulation produced no change i n vessel density of the SS group fed a 0.4% salt diet (change 5.50% and 8.1 4% 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 th e renin-angiotensin system by lisinopril or high salt restored the response s observed in the SS group fed a low salt diet. In addition, increases in V EGF 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.