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Pulmonary arterial hypoxic contraction: signal transduction
N Jin1, C S Packer, R A Rhoades
1Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46202.
The American Journal of Physiology
|July 1, 1992
Summary
Hypoxia causes a biphasic response in rat pulmonary arteries. Endothelial cells are required for the initial contraction, while calcium and protein kinase C mediate the sustained phase.
Area of Science:
- Physiology
- Pharmacology
- Vascular Biology
Background:
- Acute hypoxia elicits a biphasic contraction in isolated rat pulmonary arteries.
- This response includes an initial rapid contraction and partial relaxation (phase 1), followed by a sustained contraction (phase 2).
Purpose of the Study:
- To investigate the role of endothelium-derived products in hypoxic pulmonary arterial contraction.
- To determine if calcium and protein kinase C are second messengers in this process.
- To identify mediators of phase 1 relaxation, including cGMP, EDRF, PGI2, and adenosine receptor activation.
Main Methods:
- Isolated rat pulmonary artery preparations were subjected to acute hypoxia.
- Experiments involved Ca(2+)-free media, verapamil, ryanodine, and protein kinase C inhibitor H-7.
- Endothelium removal and blockade of specific signaling pathways (cGMP, EDRF, PGI2, adenosine) were employed.
Main Results:
- Phase 1 contraction was abolished by endothelium removal but unaffected by Ca(2+)-free media, verapamil, or ryanodine.
- Phase 2 contraction was inhibited by Ca(2+)-free media, verapamil, and H-7.
- Phase 1 relaxation was not blocked by inhibitors of guanylate cyclase, EDRF, cyclooxygenase, adenosine receptors, or K(ATP) channels.
Conclusions:
- Endothelial cells are essential for the initial hypoxic pulmonary arterial contraction (phase 1).
- Calcium influx and protein kinase C are critical for the sustained hypoxic contraction (phase 2).
- The mediators of phase 1 relaxation remain unidentified by the tested pathways.