Altered muscle metabolism associated with vasoconstriction in spontaneously hypertensive rats.
In the rat muscle vascular bed, vasoconstrictors either increase or decrease oxygen consumption (VO2). 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, VO2, 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, VO2, and lactate production in SHR were shifted to the left compared with WKY. Associated with the increased perfusion pressure, NE-induced VO2 and glucose uptake were both decreased (P < 0.01), particularly at high concentrations. These differences were unaffected by 10 microM propranolol but were all diminished by further addition of prazosin (2.5 nM). ANG II stimulated VO2, 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 VO2 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.
Ye
J M
JM
Division of Biochemistry, School of Medicine, University of Tasmania, Hobart, Tasmania 7001, Australia.
Colquhoun
E Q
EQ
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005947:Glucose / Q000493:pharmacokinetics; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D019344:Lactic Acid / Q000096:biosynthesis; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism / Q000502:physiology*; D011921:Rats, Inbred WKY / Q000378:metabolism / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D012701:Serotonin; D019344:Lactic Acid; D011433:Propranolol; D005947:Glucose; D009638:Norepinephrine; D011224:Prazosin