Previous studies have indicated the importance of angiotensin II (ANGII) in skeletal muscle angiogenesis. The present study explored the effect of the regulation of the renin gene on angiogenesis induced by electrical stimulation, using physiological, pharmacological and genetic manipulations of the renin angiotensin system (RAS). Transfer of the entire chromosome 13, containing the physiologically regulated renin gene, from the normotensive inbred Brown Norway (BN) rat into the background of an inbred sub-strain of the Dahl salt-sensitive (SS/Mcwi) rat restored renin levels and the angiogenic response after electrical stimulation. This restored response was significantly attenuated when the SS-13BN/Mcwi consomic rats were treated with lisinopril or high salt diet. The role of ANGII on this effect was confirmed by the complete restoration of the skeletal muscle angiogenesis in SS/Mcwi rats infused with sub-pressor doses of ANGII. Congenic strains derived from the SS-13BN/Mcwi consomic were used to further verify the role of the renin gene in this response. Microvessel density was markedly increased after stimulation in congenic strains that contained the renin gene from the BN rat (congenic lines A and D). This angiogenic response was suppressed in control strains that carried regions of the BN genome just above (congenic line C) or just below the renin gene (congenic line B). The present study emphasizes the importance of maintaining normal renin regulation as well as ANGII levels during the angiogenesis process using a combination of physiological, genetic and pharmacological manipulation of the RAS.