Reduction in soluble guanylyl cyclase-specific activity following prolonged treatment of porcine pulmonary artery with nitric oxide

William J. Perkins, Miwa Taniguchi, David O. Warner, Eduardo N. Chini, Keith A. Jones

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

In a newly characterized cultured porcine pulmonary artery (PA) preparation, 24-h treatment with the nitric oxide (NO) donor (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO) decreased the response to acutely applied DETA-NO compared with 24-h control (-log EC50 6.55 ± 0.12 and 5.02 ± 0.21, respectively). Treatment of PA with the cell-permeable superoxide dismutase mimetic, Mn(III) tetra(4-benzoic acid) porphyrin chloride, did not change NO responsiveness in either freshly prepared or 24-h DETA-NO-treated PA. cGMP and cAMP phosphodiesterase activities were approximately equal in PA. Twenty-four-hour DETA-NO treatment did not change either cGMP or cAMP phosphodiesterase activities. Twenty-four hours in culture had no significant effect on soluble guanylyl cyclase (sGC) subunit mRNA expression, but 24-h DETA-NO treatment significantly decreased the expression of both sGCα1 and sGCβ1. sGCβ1 protein expression was 42 ± 4 ng/mg soluble protein. Twenty-four hours in culture without and with DETA-NO reduced sGCβ1 protein expression (36 ± 3 and 31 ± 3 ng/mg soluble protein, respectively, P < 0.025). Basal tissue cGMP [(cGMP)i] was significantly increased, and NO-induced (cGMP)i was significantly decreased by 24-h DETA-NO treatment. (cGMP)i normalized to the amount of sGC protein expressed in PA was significantly lower in PA treated for 24 h with DETA-NO compared with both freshly isolated and 24-h cultured PA. We conclude that prolonged NO treatment induces decreased acute NO responsiveness in part by decreasing both sGC expression and sGC-specific activity.

Original languageEnglish (US)
Pages (from-to)L84-L95
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume293
Issue number1
DOIs
StatePublished - Jul 2007

Keywords

  • Guanosine 3′,5′cyclic monophosphate
  • Nitric oxide
  • Pulmonary artery

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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