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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

This article has been cited by other articles:

				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]

				W. J. Perkins, D. O. Warner, and K. A. Jones Prolonged treatment of porcine pulmonary artery with nitric oxide decreases cGMP sensitivity and cGMP-dependent protein kinase specific activity Am J Physiol Lung Cell Mol Physiol, January 1, 2009; 296(1): L121 - L129. [Abstract] [Full Text] [PDF]