Skip to main content
Log in

Sildenafil, a Phosphodiesterase-5 Inhibitor, Delays Gastric Emptying and Gastrointestinal Transit of Liquid in Awake Rats

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

We studied the effect of sildenafil on gastric emptying (GE) and gastrointestinal (GI) transit in awake rats. After cervical vessel cannulation and 24 hr of fasting, the animals received an intravenous (IV) injection of sildenafil (4 mg/kg) or vehicle. Next they were gavage fed (1.5 ml) with a test meal (phenol red in 5% glucose solution, 0.5 mg/ml) and sacrificed 10, 20, or 30 min later. Experimental and control subsets consisted of 5–10 rats. Gastric and proximal, medial, and distal small intestine dye retentions (GDR and IDR, respectively) were obtained by spectrophotometry. Data were compared by ANOVA and Student-Newman-Keuls test. In sildenafil-treated animals, GDR increased (P < 0.05) by 20.3%, 46.9%, and 55,5% while medial IDR decreased (P < 0.05) by 35.1%, 43.4%, and 41.6%, respectively, at 10, 20, and 30-min intervals. Proximal and distal IDR values did not change in sildenafil-treated animals. Mean arterial pressure (MAP) decreased 25% (P < 0.05) right after sildenafil administration but normalized afterwards while in controls MAP remained unchanged. In conclusion, sildenafil delays GE and GI transit of a liquid meal while transiently decreases MAP in awake rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Goldstein I, Lue TF, Padma-Nathan H, Rosen RC, Steers WD, Wicker PA: Oral sildenafil in the treatment of erectile disfunction. N Engl J Med 338:1397-1404, 1998

    Google Scholar 

  2. Jeremy JY, Ballard AS, Naylor AM, Miller MA, Angelini GD: Effects of sildenafil, a type 5 cGMP phosphodiesterase inhibitor, and papaverine on cGMP and cAMP levels in the rabbit corpus cavernosus in vitro. Br J Urol 79:958-963, 1997

    Google Scholar 

  3. Chuang AT, Strauss JD, Murphy RA, Steers WD: Sildenafil, a type-5 cGMP phosphodiesterase inhibitor, specifically amplifies endogenous cGMP-dependent relaxation in rabbit corpus cavernosum smooth muscle in vitro. J Urol 160:257-261, 1998

    Google Scholar 

  4. Gibson A: Phosphodiesterase 5 inhibitors and nitrergic transmission—from Zaprinast to Sildenafil. Eur J Pharmacol 411:1-10, 2001

    Google Scholar 

  5. Stark ME, Szurszewski JH: Role of nitric oxide in gastro-intestinal and hepatic function disease. Gastroenterology 103:1928-1949, 1992

    Google Scholar 

  6. Sanders KM, Ward SM: Nitric oxide as a mediator of non-adrenergic non-cholinergic neurotransmission. Am J Physiol 262:G379-G392, 1992

    Google Scholar 

  7. Du C, Murray J, Bates JN, Conklin JL: Nitric oxide: mediator of NANC hyperpolarization of opossum esophageal smooth muscle. Am J Physiol 261:G1012-G1016, 1991

    Google Scholar 

  8. Beavo JA: Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol Rev 75:725-748, 1995

    Google Scholar 

  9. Zhang X, Tack J, Janssens J, Sifrim D: Effect of sildenafil, a phosphodiesterase-5 inhibitor, on oesophageal peristalsis and lower oesophageal sphincter function in cats. Neurogastroenterol Motil 13:325-331, 2001

    Google Scholar 

  10. Bortolotti M, Mari C, Lopilato C, La Rovere L, Miglioli M: Sildenafil inhibits gastroduodenal motility. Aliment Pharmacol Ther 15:157-161, 2001

    Google Scholar 

  11. Haba T, Sarna SK: Regulation of gastroduodenal empyting of solids by gastroduodenal contractions. Am J Physiol 264:G261-G271, 1993

    Google Scholar 

  12. Rosalmeida MC, Araújo PV, Saraiva LDS, Graça JRV, Ivo BB, Nóbrega MV, Clemente CM, Magalhães PJC, Rola FH, Santos AA: In vitro and in vivo effects of sildenafil on gut motility in rats. Neurogastroenterol Motil 14:589, 2002

    Google Scholar 

  13. Reynell PC, Spray GH: The simultaneous measurement of absorption and transit in the gastrointestinal tract of the rat. J Physiol 131:452-462, 1956

    Google Scholar 

  14. Gondim FA, Oliveira GR, Graça JRV, Gondim RBM, Alencar HMP, Dantas RP, Santos AA, Rola FH: Neural mechanisms involved in the delay of gastric emptying of liquid elicited by acute blood volume expansion in awake rats. Neurogastroenterol Motil 12:93-99, 1999

    Google Scholar 

  15. Gondim F de AA, Rodrigues CL, Graça JR, Camurça FD, Alencar HM, Santos AA, Rola FH: Neural mechanisms involved in the delay of gastric emptying and gastrointestinal transit of liquid after thoracic spinal cord transection in awake rats. Auton Neurosci 87:52-58, 2001

    Google Scholar 

  16. Dundore RL, Habeeb PG, Pratt PF, Becker LT, Clas DM, Buchholz RA: Differential hemodynamic responses to selective inhibitors of cyclic nucleotide phosphodiesterases in conscious rats. J Cardiovasc Pharmacol 19:937-944, 1992

    Google Scholar 

  17. Sharma RK: Study of gastric and intestinal motility in young and adult rats. Indian J Med Res 78:713-723, 1983

    Google Scholar 

  18. Rhee PL, Hyun JG, Lee JH, Kim YH, Son HJ, Kim JJ, Paik SW, Rhee JC, Choi KW: The effect of sildenafil on lower esophageal sphincter and body motility in normal male adults. Am J Gastroenterol 96:3251-3257, 2001

    Google Scholar 

  19. Tottrup A, Glavind EB, Svane D: Involvement of the L-arginine-nitric oxide pathway in internal anal sphincter relaxation. Gastroenterology. 102:409-415, 1992

    Google Scholar 

  20. Anand N, Paterson WG: Role of nitric oxide in esophageal peristalsis. Am J Physiol 226:G123-G131, 1994

    Google Scholar 

  21. Desai KM, Sessa WC, Vane JR: Involvement of nitric oxide in the reflex relaxation of the stomach to accommodate food or fluid. Nature 351:477-479, 1991

    Google Scholar 

  22. Russo A, Fraser R, Adachi K, Horowitz M, Boeckxstaens G: Evidence that nitric oxide mechanisms regulate small intestinal motility in humans. Gut 44:72-76, 1999

    Google Scholar 

  23. Maczka M, Thor P, Lorens K, Konturek SJ: Nitric oxide inhibits the myoelectric activity of the small intestine in dogs. J Physiol Pharmacol 44:31-42, 1993

    Google Scholar 

  24. Sarna SK, Otterson MF, Ryan RP, Cowles VE: Nitric oxide regulates migrating motor complex cycling and postprandial disruption. Am J Physiol 265:G759-G766, 1993

    Google Scholar 

  25. Rodriguez-Membrilla A, Marinez V, Jimenez M, Gonalons E, Vergara P: Is nitric oxide the final mediator regulating the migrating myoelectric complex cycle? Am J Physiol 268:G207-G207, 1995

    Google Scholar 

  26. Ballard SA, Gingell CJ, Tang K, Turner LA, Price ME, Naylor AM: Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. J Urol 159:2164-2171, 1998

    Google Scholar 

  27. Boolell M, Gepi-Attee S, Gingell JC, Allen MJ: Sildenafil, a novel effective oral therapy for male erectile dysfunction. Br J Urol 18:47-52, 1996

    Google Scholar 

  28. Sun WM, Doran S, Jones KL, Ooi E, Boeckxstaens G, Hebbard GS, Lingenfelser T, Morley JE, Dent J, Horowitz M: Effects of nytroglicerin on liquid gastric emptying and antropyloroduodenal motility. Am J Physiol 275:G1173-G1178, 1998

    Google Scholar 

  29. Allescher HD, Tougas G, Vergara P, Lu S, Daniel EE: Nitric oxide as a putative nonadrenergic noncholinergic inhibitory transmitter in the canine pylorus in vivo. Am J Physiol 262:G695-G695, 1992

    Google Scholar 

  30. Vobig MA: Retinal side-effects of sildenafil. Lancet 353:1442, 1999

    Google Scholar 

  31. Phillips BG, Kato M, Pesek CA, Winnicki M, Narkiewicz K, Davison D, Somers VK: Sympathetic activation by sildenafil. Circulation 102:3068-3073, 2000

    Google Scholar 

  32. Ishiguchi T, Nishioka S, Takahashi T: Inhibitory neural pathway regulating gastric emptying in rats. J Aut Nerv Syst 79:45-51, 2000

    Google Scholar 

  33. Goldenberger MM: Safety and efficacy of sildenafil citrate in the treatment of male erectile dysfunction. Clin Ther 20:1033-1048, 1998

    Google Scholar 

  34. Rendell MS, Raifer J, Wicker PA, Smith MD. Sildenafil for treatment of erectile dysfunction in men with diabetes.a randomized controlled trial. J Am Med Assoc 281:421-426, 1999

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Armenio Aguiar dos Santos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

de Rosalmeida, M.C., Saraiva, L.D.S., da Graça, J.R.V. et al. Sildenafil, a Phosphodiesterase-5 Inhibitor, Delays Gastric Emptying and Gastrointestinal Transit of Liquid in Awake Rats. Dig Dis Sci 48, 2064–2068 (2003). https://doi.org/10.1023/A:1026151227729

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026151227729

Navigation