Effects of oxygen tension on energetics of cultured vascular smooth muscle.
Chronic hypoxia is a clinically important condition known to cause vascular abnormalities. To investigate the cellular mechanisms involved, we kept rings of a rat tail artery for 4 days in hypoxic culture (HC) or normoxic culture (NC) (PO(2) = 14 vs. 110 mmHg) and then measured contractility, oxygen consumption (JO(2)), and lactate production (J(lac)) in oxygenated medium. Compared with fresh rings, basal ATP turnover (J(ATP)) was decreased in HC, but not in NC, with a shift from oxidative toward glycolytic metabolism. JO(2) during mitochondrial uncoupling was reduced by HC but not by NC. Glycogen stores were increased 40-fold by HC and fourfold by NC. Maximum tension in response to norepinephrine and the JO(2) versus tension relationship (JO(2) vs. high K(+) elicited force) were unaffected by either HC or NC. Force transients in response to caffeine were increased in HC, whereas intracellular Ca(2+) wave activity during adrenergic stimulation was decreased. Protein synthesis rate was reduced by HC. The results show that long-term hypoxia depresses basal energy turnover, impairs mitochondrial capacity, and alters Ca(2+) homeostasis, but does not affect contractile energetics. These alterations may form a basis for vascular damage by chronic hypoxia.
Lindqvist
Anders
A
Department of Physiological Sciences, Lund University, S-221 84 Lund, Sweden.
Dreja
Karl
K
Swärd
Karl
K
Hellstrand
Per
P
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000172:deficiency / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology; D010101:Oxygen Consumption; D014176:Protein Biosynthesis; D051381:Rats; D013623:Tail / Q000098:blood supply; D014475:Uncoupling Agents / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D014475:Uncoupling Agents; D014662:Vasoconstrictor Agents; D019344:Lactic Acid; D006003:Glycogen; D005947:Glucose; D010100:Oxygen; D009638:Norepinephrine