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This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/L84    most recent 00368.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Perkins, W. J. Articles by Jones, K. A. Search for Related Content PubMed PubMed Citation Articles by Perkins, W. J. Articles by Jones, K. A.

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

¹Departments of Anesthesiology, and Physiology and Biophysics, Mayo Clinic College of Medicine, Rochester, Minnesota; and ²Department of Anesthesiology, Nagasaki University School of Medicine, Nagasaki, Japan

Submitted 18 September 2006 ; accepted in final form 21 March 2007

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 sGC₁ and sGC₁. sGC₁ protein expression was 42 ± 4 ng/mg soluble protein. Twenty-four hours in culture without and with DETA-NO reduced sGC₁ 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.

nitric oxide; guanosine 3',5'-cyclic monophosphate; pulmonary artery