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NO responsiveness in pulmonary artery and airway smooth muscle: the role of cGMP regulation

¹Departments of Anesthesiology, and Physiology and Biophysics, Mayo Clinic College of Medicine, Rochester, Minnesota; and ²Department of Anesthesia and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea

Submitted 25 April 2005 ; accepted in final form 12 August 2005

The purpose of this study was to assess intrinsic smooth muscle mechanisms contributing to greater nitric oxide (NO) responsiveness in pulmonary vascular vs. airway smooth muscle. Canine pulmonary artery smooth muscle (PASM) and tracheal smooth muscle (TSM) strips were used to perform concentration response studies to an NO donor, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO). PASM exhibited a greater NO responsiveness whether PASM and TSM were contracted with receptor agonists, phenylephrine and acetylcholine, respectively, or with KCl. The >10-fold difference in NO sensitivity in PASM was observed with both submaximal and maximal contractions. This difference in NO responsiveness was not due to differences in endothelial or epithelial barriers, since these were removed, nor was it due to the presence of cGMP-independent NO-mediated relaxation in either tissue. At equal concentrations of NO, the intracellular cGMP concentration ([cGMP]_i) was also greater in PASM than in TSM. Phosphodiesterase (PDE) inhibition using isobutylmethylxanthine indicated that the greater [cGMP]_i in PASM was not due to greater PDE activity in TSM. Expression of soluble guanylate cyclase (sGC) subunit mRNA (2 ± 0.2 and 1.3 ± 0.2 attomol/µg total RNA, respectively) and protein (47.4 ± 2 and 27.8 ± 3.9 ng/mg soluble homogenate protein, respectively) was greater in PASM than in TSM. sGC₁ and sGC₁ mRNA expression was equal in PASM but was significantly different in TSM, suggesting independent regulation of their expression. An intrinsic smooth muscle mechanism accounting for greater NO responsiveness in PASM vs. TSM is greater sGC activity.

nitric oxide; soluble guanylate cyclase; guanosine 3',5'-cyclic monophosphate; phosphodiesterase; pulmonary artery; airway smooth muscle; molecular sequence data

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				W. J. Perkins, S. Kost, and M. Danielson Prolonged NO treatment decreases {alpha}-adrenoreceptor agonist responsiveness in porcine pulmonary artery due to persistent soluble guanylyl cyclase activation Am J Physiol Lung Cell Mol Physiol, April 1, 2009; 296(4): L666 - L673. [Abstract] [Full Text] [PDF]

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