Microvascular rarefaction (loss of functional capillaries) may contribute to a decline in skeletal muscle performance accompanying cardiac and vascular diseases. It is not clear to what extent loss of microvascular density occurs in the earliest stages of these conditions, if impaired arterial blood flow delivery to muscle is an aggravating factor, and whether muscle remodeling via angiogenic therapies can restore performance. Therefore, we have characterised muscle performance, arterial blood flow and microvascular perfusion and how these change when the muscle is functionally overloaded in a rat model of compensatory cardiac hypertrophy. Effects of cardiac hypertrophy on peripheral blood flow and muscle function were investigated by surgical implantation (isoflurane anaesthesia) of a titanium band to effect abdominal aortic stenosis, with determination of acute (Aob-acute; n=6) and chronic (Aob; n=7) effects after 4 weeks. To assess adaptive remodeling, a third group (Aob+OV; n=7) underwent a 2-week overload (by removal of a synergist muscle) of the extensor digitorum longus (EDL), while another overload group (OV; n=6) was otherwise intact. Bilateral EDL twitch force and fatigue-resistance were determined by indirect stimulation at 10Hz to elicit maximal isometric contractions for 180s. Carotid pressure (mmHg) and bilateral femoral artery flow (ml.min-1) were monitored. Histological assessment of cryosections enabled calculation of functional rarefaction by comparison of fluorescent Dextran (perfused) and lectin (total) labelled capillary density. Aortic banding was associated with hypertension (mean±SE: Aob-acute:140±5; Aob:157±10; Aob+OV:147±4) compared to control (122±1 mmHg, P<0.05). Increased heart mass (% body mass) was confirmed post-mortem in Aob (0.36±0.03) and Aob+OV (0.31±0.01) (P<0.05 vs. control 0.26±0.004, n=7). Fatigue index (FI: max. force at end/start of stimulation) in control was 49±6%, but was reduced in Aob-acute (24±12%; P<0.001) and Aob (37±5%; P=0.048). FI was restored to control levels in Aob+OV (49±8%; P=0.99), while a similar proportional improvement above control occurred in OV (61±7%; P=0.03). Reduced femoral blood flow occurred in Aob-acute (P<0.001) but was similar to controls in other groups, indicating that arterial perfusion did not constrain muscle performance following intervention. Reduced (P<0.05) perfused CD occurred after stenosis (control:548±37; Aob:232±14; Aob+OV:349±49; OV:556±84 mm-2), indicating a potential microvascular limitation on muscle performance. Within banded animals, functional overload stimulated an improved (P<0.01) perfused and total (Aob:565±30; Aob+OV:722±47) CD, indicating that angiogenic capacity remained despite the systemic effects of aortic stenosis. These data show that deleterious effects of cardiac hypertrophy can be countered by a non-pharmacological angiogenic intervention, providing a future therapeutic target for improving the symptoms of patients with chronic heart failure.