| Vardenafil-induced relaxation and cyclic nucleotide levels in normal and obstructed rat urinary bladder. | |
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MedLine Citation:
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PMID: 19694713 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To study the effects of the phosphodiesterase-5 inhibitor, vardenafil, on contraction and cyclic nucleotide levels in isolated detrusor preparations with and without mucosa, from control rats and rats with partial urethral obstruction (PUO) and intact mucosa. MATERIALS AND METHODS: Female Sprague-Dawley rats were divided into groups subjected to PUO for 14 days (six), and sham-operated control rats (12). Detrusor preparations were mounted in organ baths and effects of increasing concentrations of vardenafil (1 nm to 100 microm) assessed on carbachol-activated (1 microm) preparations, and on contractions induced by transmural activation of nerves (electrical field stimulation, EFS). Levels of cGMP and cAMP were determined using radioimmunoassays. RESULTS: Vardenafil caused concentration-dependent relaxations of carbachol-contracted detrusor, the mean (sd) of which at 100 microm was 91 (4)% in control and 100% in PUO rats. The -log 50% inhibitory concentration (IC(50)) was 4.41 (0.08) and 4.73 (0.05) (P < 0.01), respectively. Removing the mucosa increased the relaxant effect of vardenafil at 1-10 microm (P < 0.05) although -log IC(50) values were unaffected compared to the control. The cGMP levels ( pmol/mg protein) in control preparations increased from 2.5 (0.6) to 5.0 (0.8), and from 1.4 (0.2) to 7.2 (1.3) in obstructed bladders. In mucosa-denuded preparations the cGMP content increased from 0.6 (0.1) to 1.6 (0.4) in response to vardenafil. In control rats, the levels of cAMP increased from 12.8 (2.5) to 18.9 (0.9) (P < 0.05) after vardenafil. In mucosa-denuded preparations the cAMP levels after vardenafil increased from 16.5 (2.11) to 37.8 (3.4) (P < 0.01). In PUO bladders, the tissue content of cAMP increased from 12.6 (2.4) to 20.6 (3.4) (P < 0.01). Vardenafil concentration-dependently inhibited nerve-induced contractions in all groups studied. At 100 microm 19 (3)% of the control contraction remained, vs 8 (1)% for preparations from obstructed rats, and 11 (4)% in mucosa-denuded preparations. CONCLUSION: In normal rats, vardenafil relaxed carbachol- and inhibited EFS-induced contractions of detrusor preparations with and without urothelium, and in PUO rats with urothelium. Relaxations were accompanied by increases in both cAMP and cGMP content. It is proposed that vardenafil-induced relaxation of rat detrusor, also in obstructed and mucosa-denuded preparations, is mediated via cAMP. |
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Authors:
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Viktoria Werkstr?m; Petter Hedlund; Tack Lee; Karl-Erik Andersson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-08-19 |
Journal Detail:
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Title: BJU international Volume: 104 ISSN: 1464-410X ISO Abbreviation: BJU Int. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2010-01-07 Completed Date: 2010-02-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100886721 Medline TA: BJU Int Country: England |
Other Details:
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Languages: eng Pagination: 1740-5 Citation Subset: IM |
Affiliation:
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Department of Clinical and Experimental Pharmacology, Institute for Laboratory Medicine, Lund University Hospital, Lund, Sweden. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cyclic AMP / metabolism* Cyclic GMP / metabolism* Female Imidazoles / pharmacology* Muscle Relaxation / drug effects Muscle, Smooth / drug effects Phosphodiesterase Inhibitors / pharmacology* Piperazines / pharmacology* Rats Rats, Sprague-Dawley Sulfones / pharmacology Triazines / pharmacology Urethral Obstruction / drug therapy*, metabolism, physiopathology Urinary Bladder / drug effects*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Imidazoles; 0/Phosphodiesterase Inhibitors; 0/Piperazines; 0/Sulfones; 0/Triazines; 224785-90-4/vardenafil; 60-92-4/Cyclic AMP; 7665-99-8/Cyclic GMP |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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