Document Detail


Inhibitory effect of sildenafil on rat duodenal contractility in vitro: putative cGMP involvement.
MedLine Citation:
PMID:  15743402     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. Sildenafil citrate (Viagratrade mark; Pfizer, Sandwich, Kent, UK), a phosphodiesterase 5 inhibitor, rises cGMP levels in smooth muscle cells. It relaxes both vascular and visceral smooth muscle. In order to assess the intestinal effects of sildenafil, we decided to investigate its actions on rat duodenal motor activity in vitro. 2. In isolated duodenal segments maintained in Tyrode's solution, sildenafil exhibited a concentration-dependent antispasmodic effect on acetylcholine (ACh)-induced phasic contractions, with an IC50 value of 26.7 micromol/L (95% confidence interval (CI) 2.0-55.3 micromol/L). 3. Sildenafil also relaxed the carbamylcholine (CCh)-induced sustained contraction with an IC(50) of 16.2 micromol/L (95% CI 9.5-27.6 micromol/L). Sildenafil produced significant additional relaxation of 25.2 +/- 8.1% of the CCh-induced contraction, beyond basal tone. 4. Sildenafil reduced the amplitude of spontaneous duodenal contractions with an EC50 of 9.6 micromol/L (95% CI 5.7-16.2 micromol/L). This effect was significantly more potent than the effects of zaprinast and papaverine, which also reduced duodenal contractions with EC50 values of 91.6 micromol/L (95% CI 46.0-182.2 micromol/L) and 78.5 micromol/L (95% CI 37.1-166.3 micromol/L), respectively. 5. In preparations treated previously with methylene blue (10 micromol/L) or 1H-[1,2,4]oxadiazolo(4,3-a)quinoxalin-1-one (ODQ; 10 micromol/L), the EC50 values for the sildenafil effect were significantly increased to 39.0 micromol/L (95% CI 23.9-63.4 micromol/L) and 43.8 micromol/L (95% CI 24.5-78.3 micromol/L), respectively. These values were significantly greater than those obtained with sildenafil alone. 6. In conclusion, sildenafil has myorelaxant and antispasmodic effects on rat duodenal segments in vitro. The contractile inhibitory effect of sildenafil on rat isolated duodenum is probably due to intracellular cGMP accumulation as a result of its decreased degradation.
Authors:
Paula Vasconcelos Araújo; Cristiano Magalhães Clemente; José Ronaldo Vasconcelos da Graça; Francisco Hélio Rola; Ricardo Brandt de Oliveira; Armênio Aguiar dos Santos; Pedro Jorge Caldas Magalhães
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  32     ISSN:  0305-1870     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-03-03     Completed Date:  2005-06-22     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  191-5     Citation Subset:  IM    
Affiliation:
Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
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MeSH Terms
Descriptor/Qualifier:
Animals
Depression, Chemical
Duodenum / drug effects*,  physiology
Guanylate Cyclase / antagonists & inhibitors
Male
Muscle Contraction / drug effects
Muscle, Smooth / drug effects*,  physiology
Phosphodiesterase Inhibitors / pharmacology*
Piperazines / pharmacology*
Purines
Rats
Rats, Wistar
Sulfones
Chemical
Reg. No./Substance:
0/Phosphodiesterase Inhibitors; 0/Piperazines; 0/Purines; 0/Sulfones; 139755-83-2/sildenafil; EC 4.6.1.2/Guanylate Cyclase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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