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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.
Am J Gastroenterol. 2003 Oct; 98(10):2253-60.AJ

Abstract

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.

Authors+Show Affiliations

Universitätsklinik für Innere Medizin IV, Abteilung für Gastroenterologie und Hepatologie, University of Vienna, Vienna, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

14572576

Citation

Fritz, Eva, et al. "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." The American Journal of Gastroenterology, vol. 98, no. 10, 2003, pp. 2253-60.
Fritz E, Hammer J, Schmidt B, et al. 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. Am J Gastroenterol. 2003;98(10):2253-60.
Fritz, E., Hammer, J., Schmidt, B., Eherer, A. J., & Hammer, H. F. (2003). 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. The American Journal of Gastroenterology, 98(10), 2253-60.
Fritz E, et al. 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. Am J Gastroenterol. 2003;98(10):2253-60. PubMed PMID: 14572576.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Fritz,Eva, AU - Hammer,Johann, AU - Schmidt,Barbara, AU - Eherer,Andreas J, AU - Hammer,Heinz F, PY - 2003/10/24/pubmed PY - 2003/12/3/medline PY - 2003/10/24/entrez SP - 2253 EP - 60 JF - The American journal of gastroenterology JO - Am J Gastroenterol VL - 98 IS - 10 N2 - 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. SN - 0002-9270 UR - https://www.unboundmedicine.com/medline/citation/14572576/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_ L2 - https://Insights.ovid.com/pubmed?pmid=14572576 DB - PRIME DP - Unbound Medicine ER -