Skeletal muscle responds to endurance exercise with an improvement of biochemical pathways that support substrate supply and oxygen‐dependent metabolism. This is reflected by enhanced expression of associated factors after exercise and is specifically modulated by tissue perfusion and oxygenation. We hypothesized that transcript expression of pro‐angiogenic factors (VEGF, tenascin‐C, Angpt1, Angpt1R) and oxygen metabolism (COX4I1, COX4I2, HIF‐1α) in human muscle after an endurance stimulus depends on vasoconstriction, and would be modulated through angiotensin‐converting enzyme inhibition by intake of lisinopril. Fourteen non‐specifically trained, male Caucasians subjects, carried out a single bout of standardized one‐legged bicycle exercise. Seven of the participants consumed lisinopril in the 3 days before exercise. Biopsies were collected pre‐ and 3 h post‐exercise from the m. vastus lateralis. COX4I1 (P = 0.03), COX4I2 (P = 0.04) mRNA and HIF‐1α (P = 0.05) mRNA and protein levels (P = 0.01) showed an exercise‐induced increase in the group not consuming the ACE inhibitor. Conversely, there was a specific exercise‐induced increase in VEGF transcript (P = 0.04) and protein levels (P = 0.03) and a trend for increased tenascin‐c transcript levels (P = 0.09) for subjects consuming lisinopril. The observations indicate that exercise‐induced expression of transcripts involved in angiogenesis and mitochondrial energy metabolism are to some extent regulated via a hypoxia‐related ACE‐dependent mechanism.