Effect of change in oxygen tension on release pattern and nature of endothelium-derived substances in isolated rabbit aorta.
OBJECTIVE
To observe the effect of change in oxygen tension on the release pattern and nature of endothelium-derived substances in isolated rabbit aorta.


METHODS
Isometric contractions and relaxations in isolated rabbit strip were observed in response to changes in oxygen tension and effect of various drugs was noted on them.


RESULTS
Change in oxygen tension from high [pO2 =(618.9 +/- 0.4) mmHg; 1 mmHg = 133.3 Pa] to low [pO2 = (117.6+/-0.6) mmHg] was observed to convert the relaxant effect of acetylcholine (ACh), in rabbit aorta precontracted with phenylephrine, to a marked contractile response. As the aerating gas was changed from 100 % to 20 % oxygen, the relaxant effect to ACh, recorded every hour, gradually decreased till it gave way to a significant contraction over a period of 3.5 h. On reoxygenation the relaxant effect to ACh was irreversibly inhibited, however, the relaxant effect to SOD (40 kU/L) was not. The per se constrictor effect to ACh was abolished by endothelium removal and by combination of SOD (40 kU/L), catalase (1000 kU/L) and indomethacin (1 x 10(-5 ) mol/L). SQ-030741(1 x 10(-5) mol/L) or GR-32191B (1 x 10(-5) mol/L), both TXA2-PGH2 receptor antagonists but not OKY-046, a TXA2-synthetase inhibitor, also attenuated the ACh-mediated contractions in combination with SOD and catalase.


CONCLUSIONS
The above results implicate that some functional change occurs in the endothelium exposed to low p(O2) such that the stimulated release of endothelium-derived relaxing factor (EDRF) in response to ACh is completely and irreversibly inhibited, whereas, the basally released EDRF in response to SOD is not and marked increase in prostaglandin synthesis is stimulated.
Mittra
S
S
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala-147 002, India.
Singh
M
M
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000097:blood*; D010313:Partial Pressure; D011817:Rabbits; D013482:Superoxide Dismutase / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D016166:Free Radical Scavengers; D014665:Vasodilator Agents; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D000109:Acetylcholine; D010100:Oxygen