Altered muscle metabolism associated with vasoconstriction in spontaneously hypertensive rats

In the rat muscle vascular bed, vasoconstrictors either increase or decrease oxygen consumption ((V) over dotO(2)). 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, (V) over dotO(2), glucose uptake, and lactate production were increased by 21.4, 11.9, 46.4, and 44.9% (P < 0.05 far 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, (V) over dotO(2), and lactate production in SHR were shifted to the left compared with WKY. Associated with the increased perfusion pressure, NE-induced (V) over dotO(2) and glucose uptake were both decreased (P < 0.01), particularly at high concentrations. These differences were unaffected by 10 mu M propranolol but were all diminished by further addition of prazosin (2.5 nM). ANG II stimulated (V)over dotO(2), glucose uptake, and,lactate production in bath 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 (V) over dotO(2) 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.