![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
HL Zhou and TJ Torphy
Division of Pharmacological Sciences, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania.
The role of cyclic GMP (cGMP) in mediating relaxation of canine trachealis produced by nitrovasodilators (NVDs), compounds that activate guanylate cyclase, was examined. Sodium nitroprusside (SNP) produced a concentration-dependent relaxation of the canine trachealis that was accompanied by a concentration-related increase in cGMP content. In time course studies, relaxation of isolated trachealis strips induced by 30 microM SNP was paralleled by an increase in cGMP that reached a maximum of 18-fold above basal levels within 2 min. Zaprinast, an inhibitor of the cGMP-specific phosphodiesterase, potentiated both SNP-induced relaxation and cGMP accumulation. A cell- permeable analog of cGMP, 8-bromo-cGMP, mimicked the relaxant effects of SNP. Also assessed were the effects of methylene blue, an agent that inhibits soluble guanylate cyclase activity, and hemoglobin, an agent that competitively binds NO-containing compounds. In these experiments, tissues were pretreated with the above agents for 10 min, contracted with 1 or 3 microM methacholine, and then relaxed by the cumulative addition of SNP or two other NVDs, S-nitroso-N-acetyl-penicillamine (SNAP) and glyceryl trinitrate (GTN). Tissues were flash-frozen after adding the final concentration of the various NVDs and assayed for cGMP. Methylene blue and hemoglobin suppressed both cGMP accumulation and relaxation in response to SNAP and GTN. in contrast, methylene blue and hemoglobin inhibited SNP-induced cGMP accumulation but, paradoxically, potentiated SNP-induced relaxation. The results of this study generally support a role for cGMP in NVD-induced relaxation of airway smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
This article has been cited by other articles:
|
|
 |
|
  Y. L. Kwak, K. A. Jones, D. O. Warner, and W. J. Perkins NO responsiveness in pulmonary artery and airway smooth muscle: the role of cGMP regulation Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L200 - L208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Mo, H. Amin, I. H. Bianco, and J. Garthwaite Kinetics of a Cellular Nitric Oxide/cGMP/Phosphodiesterase-5 Pathway J. Biol. Chem., June 18, 2004; 279(25): 26149 - 26158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Hamad, A. Clayton, B. Islam, and A. J. Knox Guanylyl cyclases, nitric oxide, natriuretic peptides, and airway smooth muscle function Am J Physiol Lung Cell Mol Physiol, November 1, 2003; 285(5): L973 - L983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. White, T. F. Walseth, and M. S. Kannan Nitric oxide inhibits ADP-ribosyl cyclase through a cGMP-independent pathway in airway smooth muscle Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L1065 - L1071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-H. Liu, H. Jin, H. S. Floten, Z. Ren, A. P.C. Yim, and G.-W. He Vascular endothelial growth factor-mediated, endothelium-dependent relaxation in human internal mammary artery Ann. Thorac. Surg., March 1, 2002; 73(3): 819 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. H. Rho, W. J. Perkins, R. R. Lorenz, D. O. Warner, and K. A. Jones Differential effects of soluble and particulate guanylyl cyclase on Ca2+ sensitivity in airway smooth muscle J Appl Physiol, January 1, 2002; 92(1): 257 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-H. Liu, H.-K. Jin, H. S. Floten, Q. Yang, A. P. C. Yim, A. Furnary, T. F. Zioncheck, S. Bunting, and G.-W. He Vascular Endothelial Growth Factor-Mediated Endothelium-Dependent Relaxation Is Blunted in Spontaneously Hypertensive Rats J. Pharmacol. Exp. Ther., April 13, 2001; 296(2): 473 - 477. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Malysz, G. Donnelly, and J. D. Huizinga Regulation of slow wave frequency by IP3-sensitive calcium release in the murine small intestine Am J Physiol Gastrointest Liver Physiol, March 1, 2001; 280(3): G439 - G448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Janssen, M. Premji, H. Lu-Chao, G. Cox, and S. Keshavjee NO+ but not NO radical relaxes airway smooth muscle via cGMP-independent release of internal Ca2+ Am J Physiol Lung Cell Mol Physiol, May 1, 2000; 278(5): L899 - L905. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. KAWASHIMA, T. BANDO, T. NAKAMURA, N. ISOWA, M. LIU, S. TOYOKUNI, S. HITOMI, and H. WADA Cytoprotective Effects of Nitroglycerin in Ischemia-Reperfusion-Induced Lung Injury Am. J. Respir. Crit. Care Med., March 1, 2000; 161(3): 935 - 943. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Pabelick, D. O. Warner, W. J. Perkins, and K. A. Jones S-nitrosoglutathione-induced decrease in calcium sensitivity of airway smooth muscle Am J Physiol Lung Cell Mol Physiol, March 1, 2000; 278(3): L521 - L527. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Abderrahmane, D. Salvail, M. Dumoulin, J. Garon, A. Cadieux, and E. Rousseau Direct Activation of KCa Channel in Airway Smooth Muscle by Nitric Oxide: Involvement of a Nitrothiosylation Mechanism? Am. J. Respir. Cell Mol. Biol., September 1, 1998; 19(3): 485 - 497. [Abstract] [Full Text]
|
|
|
|
 |
|
 W. J. Perkins, C. Pabelick, D. O. Warner, and K. A. Jones cGMP-independent mechanism of airway smooth muscle relaxation induced by S-nitrosoglutathione Am J Physiol Cell Physiol, August 1, 1998; 275(2): C468 - C474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Hamad, S. Range, E. Holland, and A. J. Knox Regulation of cGMP by soluble and particulate guanylyl cyclases in cultured human airway smooth muscle Am J Physiol Lung Cell Mol Physiol, October 1, 1997; 273(4): L807 - L813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Ellis Role of Soluble Guanylyl Cyclase in the Relaxations to a Nitric Oxide Donor and to Nonadrenergic Nerve Stimulation in Guinea Pig Trachea and Human Bronchus J. Pharmacol. Exp. Ther., March 1, 1997; 280(3): 1215 - 1218. [Abstract] [Full Text]
|
|
|
|
|
|
T. J. TORPHY Phosphodiesterase Isozymes . Molecular Targets for Novel Antiasthma Agents Am. J. Respir. Crit. Care Med., February 1, 1997; 157(2): 351 - 370. [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
