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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

Oxygen Consumption

Oxygen : pharmacology

Oxygen : metabolism

Norepinephrine : pharmacology

Vascular : metabolism

Smooth

Muscle

Vascular : drug effects

Lactic Acid : metabolism

Intracellular Fluid : metabolism

In Vitro

Glycogen : metabolism

Glucose : metabolism

Glucose : deficiency

Female

Energy Metabolism : physiology

Tail : blood supply

Vasoconstrictor Agents : pharmacology

Vasoconstriction : physiology

Uncoupling Agents : pharmacology

Vasoconstriction : drug effects

Proteins : biosynthesis

Rats

Support

Non-U.S. Gov't

Energy Metabolism : drug effects

Cell Hypoxia : physiology

Calcium Signaling : physiology

Arteries : metabolism

Arteries : drug effects

Animal

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)