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Am J Physiol Lung Cell Mol Physiol (April 11, 2003). doi:10.1152/ajplung.00362.2002
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Submitted on October 29, 2002
Accepted on April 9, 2003

Hypoxia Enhances a cGMP-Independent Nitric Oxide Relaxing Mechanism in Pulmonary Arteries

Christopher J. Mingone1, Sachin A. Gupte1, Takafumi Iesaki1, and Michael S. Wolin1*

1 Department of Physiology, New York Medical College, Valhalla, NY, USA

* To whom correspondence should be addressed. E-mail: mike_wolin{at}nymc.edu.

NO-donors generally relax vascular preparations through cGMP-mediated mechanisms. Relaxation of endothelium-removed bovine pulmonary (BPA) and coronary arteries (BCA) to the NO-donor SNAP is almost eliminated by inhibition of soluble guanylate cyclase activation with 10 µM ODQ, whereas, only a modest inhibition of relaxation is observed under hypoxia (PO2=8-10 torr). This effect of hypoxia is independent of the contractile agent used, and is also observed with NO gas. ODQ eliminated SNAP-induced increases in cGMP under hypoxia in BPA. cGMP-independent relaxation of BPA to SNAP was not attenuated by inhibition of K+-channels (10 mM TEA), myosin light chain phosphatase (0.5 µM microcystin-LR) or adenylate cyclase (4 µM 2',5'-dideoxyadenosine). SNAP relaxed BPA contracted with serotonin under calcium-free conditions in the presence of hypoxia and ODQ, and contraction to calcium re-addition was also attenuated. The SR calcium-reuptake inhibitor 0.2 mM cyclopiazonic acid attenuated SNAP-mediated relaxation of BPA in the presence of ODQ. Thus, hypoxic conditions appear to promote a cGMP-independent relaxation of BPA to NO by enhancing SR calcium-reuptake.




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