Functional characteristics of urinary tract smooth muscles in mice lacking cGMP protein kinase type I

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2000-09, Vol.279 (3), p.1112-R1120
• Main Authors: Persson, Katarina, Pandita, Raj Kumar, Aszodi, Attila, Ahmad, Marianne, Pfeifer, Alexander, Fassler, Reinhard, Andersson, Karl-Erik
• Format: Article
• Language: English
• Subjects: 8-Bromo Cyclic Adenosine Monophosphate - pharmacology; Animals; Carbachol - pharmacology; Cholinergic Agonists - pharmacology; Colforsin - pharmacology; Cyclic GMP - metabolism; Cyclic GMP-Dependent Protein Kinases - analysis; Cyclic GMP-Dependent Protein Kinases - genetics; Electric Stimulation; Female; Gene Expression Regulation, Enzymologic; Immunohistochemistry; Male; Mice; Mice, Knockout; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle, Smooth - physiology; Nitric Oxide Synthase - analysis; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type I; Urethra - physiology; Urinary Bladder - physiology
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.2000.279.3.r1112

Departments of 1  Clinical Pharmacology and 2  Experimental Pathology, University of Lund, S-221 85 Lund, Sweden; and 3  Salk Institute, La Jolla, California 92037 Nitric oxide (NO)-mediated smooth muscle relaxation is mediated by cGMP through activation of cGMP-dependent protein kinase I (cGKI). We studied the importance of cGKI for lower urinary tract function in mice lacking the gene for cGKI (cGKI / ) and in litter-matched wild-type mice (cGKI+/+) in vitro and in vivo. cGKI deficiency did not result in any changes in bladder gross morphology or weight. Urethral strips from cGKI / mice showed an impaired relaxant response to nerve-derived NO. The cGMP analog 8-bromo-cGMP (8-BrcGMP) and the NO-donor SIN-1 relaxed the wild-type urethra (50-60%) but had only marginal effects in the cGKI-deficient urethra. Bladder strips from cGKI / mice responded normally to electrical field stimulation and to carbachol but not to 8-BrcGMP. In vivo, the cGKI-deficient mice showed bladder hyperactivity characterized by decreased intercontraction intervals and nonvoiding bladder contractions. Loss of cGKI abolishes NO-cGMP-dependent relaxations of urethral smooth muscle and results in hyperactive voiding. These data suggest that certain voiding disturbances may be associated with impaired NO-cGKI signaling. nitric oxide synthase; transgenic; urethra; bladder; nonadrenergic, noncholinergic