Document Detail

Stimulation of the nitric oxide-guanosine 3', 5'-cyclic monophosphate pathway by sildenafil: effect on rectal muscle tone, distensibility, and perception in health and in irritable bowel syndrome.
MedLine Citation:
PMID:  14572576     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: Nitric oxide, a neurotransmitter in the noncholinergic, nonadrenergic nervous system, is a mediator of relaxation of GI smooth muscle and of visceral nociception mainly studied in vitro. Sildenafil stimulates the nitric oxide guanosine 3', 5'-cyclic monophosphate (NO-cGMP) pathway through inhibition of phosphodiesterase 5. The aims of this study were to evaluate in vivo the effect of stimulation of the NO-cGMP pathway on rectal tone, distensibility, and perception in healthy individuals and in patients with irritable bowel syndrome (IBS). METHODS: In eight healthy subjects and four patients with IBS rectal tone, distensibility and perception thresholds were measured with an electronic barostat both before and 60 min after administration of sildenafil (50 mg p.o.). Perception was scored on a graded scale of 0-6. At the end of a distension series an anatomic questionnaire was filled out by the subjects. RESULTS: Sildenafil significantly reduced rectal tone in healthy subjects (intrabag volume predrug: 145.5 +/- 18.7 ml vs postdrug: 164.4 +/- 16.9 ml, p = 0.01) and IBS (111.3 +/- 25.2 ml vs 136.5 +/- 33.3 ml; p = 0.01) but did not alter rectal compliance (healthy subjects: 5.8 +/- 0.4 vs 6.3 +/- 0.6 ml/mm Hg, p > 0.05; IBS subjects: 6.1 +/- 0.6 vs 7.1 +/- 1.0 ml/mm Hg, p > 0.05). Intrabag pressure and rectal wall tension to reach perception thresholds for initial sensation, sensation of stool, and urgency were not altered by sildenafil. However, intrabag volumes to reach these thresholds were significantly increased by sildenafil both in healthy subjects and in patients with IBS. Viscerosomatic referral was unchanged. CONCLUSIONS: Stimulation of the NO-cGMP pathway decreases rectal tone but does not influence rectal distensibility. Relaxation of the rectum is accompanied by an increase in rectal volumes to reach perception thresholds in healthy subjects and in patients with IBS, but no direct effect on rectal perception can be demonstrated.
Eva Fritz; Johann Hammer; Barbara Schmidt; Andreas J Eherer; Heinz F Hammer
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  The American journal of gastroenterology     Volume:  98     ISSN:  0002-9270     ISO Abbreviation:  Am. J. Gastroenterol.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-10-23     Completed Date:  2003-11-26     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0421030     Medline TA:  Am J Gastroenterol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2253-60     Citation Subset:  IM    
Universitätsklinik für Innere Medizin IV, Abteilung für Gastroenterologie und Hepatologie, University of Vienna, Vienna, Austria.
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MeSH Terms
Case-Control Studies
Cyclic GMP / metabolism*
Intestinal Mucosa / drug effects
Irritable Bowel Syndrome / diagnosis,  drug therapy*
Middle Aged
Muscle Tonus / drug effects*,  physiology
Nitric Oxide / metabolism*
Piperazines / administration & dosage*
Prospective Studies
Rectum / drug effects*,  physiology
Reference Values
Sensitivity and Specificity
Sensory Thresholds
Severity of Illness Index
Statistics, Nonparametric
Reg. No./Substance:
0/Piperazines; 0/Purines; 0/Sulfones; 10102-43-9/Nitric Oxide; 139755-83-2/sildenafil; 7665-99-8/Cyclic GMP

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