In the rat muscle vascular bed, vasoconstrictors either increase or decrease oxygen consumption (O₂). The present study compared the effects of norepinephrine (NE), angiotensin II (ANG II), and 5-hydroxytryptamine (5-HT) on vasoconstriction-associated metabolism in the constant-flow perfused hindlimb of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) in the absence of insulin. Basal perfusion pressure, O₂, glucose uptake, and lactate production were increased by 21.4, 11.9, 46.4, and 44.9% (P < 0.05 for all), respectively, in SHR, which also had higher blood pressure and metabolic rate (P < 0.05) in vivo. Dose-response curves for NE-induced perfusion pressure, O₂, and lactate production in SHR were shifted to the left compared with WKY. Associated with the increased perfusion pressure, NE-induced O₂ and glucose uptake were both decreased (P < 0.01), particularly at high concentrations. These differences were unaffected by 10 µM propranolol but were all diminished by further addition of prazosin (2.5 nM). ANG II stimulated O₂, glucose uptake, and lactate production in both strains, but the increased lactate production was smaller in SHR (P < 0.05) with a proportional decrease (P < 0.05) in glucose uptake. Conversely, 5-HT decreased O₂ in both strains (P < 0.01), and this effect was greater in SHR (P < 0.01). These data suggest that SHR muscle thermogenesis and glucose uptake are impaired during vasoconstriction, especially in response to NE.