Hypoxic contractile response in isolated rat thoracic aorta: role of endothelium, extracellular calcium and endothelin

The effects of hypoxia on isolated arteries remain controversial, depending on the species, vascular beds and protocols. The aims of the study were to characterize the response of rat thoracic aorta to hypoxia and to examine the roles of endothelium, extracellular calcium and endothelin in this response. Hypoxia was induced by bubbling Krebs solution with 95% N2 and 5% CO2 instead of 95% O2 and 5% CO2. Experiments were performed during 1 h in norepinephrine (0.01 microM) precontracted rings. Hypoxia produced a biphasic response consisting of an initial transient partial relaxation (67% at 14 min) followed by a slow but sustained contraction (27% from 40 to 60 min). After endothelium removal, relaxation appeared faster with increased magnitude (82% at 12 min) and was followed by a weak transient contraction (16% at 25 min). In endothelium-intact rings, Ca2+ free medium (EGTA, 0.1 mM) and Ca2+ channel blockers, verapamil (0.05, 0.5 and 5 microM) or nicardipine (0.1, 1 and 10 microM), had no effect on relaxation but inhibited the contraction, the effects of both calcium antagonists being concentration-dependent. Similarly, the ETA/ETB receptor antagonist, bosentan (0.1, 10 and 1,000 nM), induced a concentration-dependent decrease in the contraction. We conclude that 1) the response of rat thoracic aorta during 1 h of hypoxia is biphasic (relaxation followed by contraction); 2) the endothelium is involved in the contraction whereas its role in the relaxation remains to be elucidated; 3) extracellular calcium is involved in the contraction; and 4) endothelin may play a role in the contraction.