Submitted on September 19, 2005
Accepted on November 29, 2005
Nitric Oxide Sensitivity in Pulmonary Artery and Airway Smooth Muscle: A Possible Role for cGMP Responsiveness
Miwa Taniguchi1, Young Lan Kwak2, Keith A Jones3, David O Warner3, and William J Perkins3*
1 Department of Anesthesia, Nagasaki University School of Medicine, Nagasaki, Japan
2 Department of Anesthesia and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea
3 Departments of Anesthesiology, and Physiology and Biophysics, Mayo Clinic College of Medicine, Rochester, MN, USA
* To whom correspondence should be addressed. E-mail: perkinsw{at}mayo.edu.
The purpose of this study was to assess intrinsic smooth muscle mechanisms contributing to greater NO responsiveness in pulmonary vascular versus airway smooth muscle. Porcine pulmonary artery smooth muscle (PASM) and tracheal smooth muscle (TSM) strips were used to perform concentration response studies to the NO-donor, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO). PASM consistently exhibited greater relaxation at a given [DETA-NO] (NO responsiveness) than TSM NO responsiveness with the DETA-NO log EC50 -6.55 ± 0.11 and -5.37 ± 0.13 for PASM and TSM, respectively, P < 0.01). The relationship between tissue cGMP ([cGMP]i) and relaxation was determined using the particulate guanylyl cyclase agonist, atrial natriuretic peptide (ANP). ANP resulted in nearly complete relaxation with no detectable increase in [cGMP]i in PASM and only 20% relaxation with a 10-fold increase in [cGMP]i in TSM, indicating that TSM is less cGMP responsive than PASM. Total cGMP-dependent protein kinase I (cGKI) mRNA expression was greater in PASM than in TSM (2.23 ± 0.36 versus 0.93 ± 0.31 attomoles mRNA/µg total RNA, respectively, P < 0.01), but total cGKI protein expression was not significantly different (0.56 ± 0.07 and 0.49 ± 0.04 ng cGKI/µg protein, respectively). The phosphotransferase assay for the soluble fraction of tissue homogenates demonstrated no difference in the cGMP EC50 between PASM and TSM. The maximal phosphotransferase activity indexed to the amount of total cGKI in the homogenate differed significantly between PASM and TSM (1.61 ± 0.15 and 1.04 ± pmol.min-1.ng cGKI-1, respectively, P < 0.05). The suffests that cGKI may be regulated in the two tissues. A novel intrinsic smooth muscle mechanism accounting for greater NO responsiveness in PASM versus TSM is thus greater cGMP responsiveness due to increased cGKI specific activity in PASM.
