(sildenafil citrate)


Viagra, Revatio


  • Tablets: 20 mg, 25 mg, 50 mg
    Can be made into a suspension


In rats, inflammation caused by chronic respiratory disease often contributes to pulmonary fibrosis and pulmonary hypertension. We observe signs of this in the aging rat as increased respiratory rate, increased respiratory effort, open-mouthed breathing, and/or extending of the head/neck when breathing, decreased appetite and/or anorexia.

Sildenafil citrate is a phosphodiesterase-V vasodilator inhibitor that is believed to act by having a protective effect on the functional and structural changes in pulmonary vasculature and lung parenchyma. It also exhibits an anti-inflammatory effect helping to prevent further fibrosis and the thickening of the airway in the lungs.1 This in turn aids in reducing further long-term changes in the lungs of rats with chronic respiratory disease with or without concurrent right sided heart disease.

The drug is designed to block the enzyme phosphodiesterase-V (PDE5) so that blood vessels in the lungs are able to dilate. Pulmonary hypertension (elevated blood pressure in the lungs) occurs when the arteries in the lungs become narrowed which elevates blood pressure, as occurs in rats with chronic respiratory disease. This causes the heart to work harder to get blood flow to the arteries in the lungs. Sildenafil dilates those blood vessels, so it is easier for the blood carrying oxygen to get to the lungs. This slows the progression of further chronic changes while also reducing symptoms noted above.

Sildenafil is rapidly absorbed following administration. It is widely distributed into body tissue. The drug is primarily metabolized via the liver and excreted in feces with a small percentage excreted in urine.

No evidence of teratogenicity, embryotoxicity, or fetotoxicity has been observed in rats at dosages of 200mg/kg/day.3 However, uses in the pregnant or nursing doe are not advised as studies have not indicated whether sildenafil is excreted in breast milk.


Used as a protective, adjunctive, treatment in rats already being treated for moderate to severe chronic respiratory disease where pulmonary hypertension is believed to be a contributing factor.

Drug Interactions or Contraindications

  • Sildenafil may increase blood levels when used with ketoconazole, itraconazole, clarithromycin and erythromycin (sildenafil appeared to be metabolized via hepatic cytochrome P450 in Sprague Dawley 5).
  • Phenobarbital may decrease the efficacy of sildenafil when used together.
  • When used with vasodilators such as: amlodipine, and nitrates, there is an increased risk for low blood pressure.
  • The clearance of sildenafil may be reduced where liver function in the rat is impaired. If liver function is impaired, a lower dose may be warranted.
  • The clearance of sildenafil may be reduced with concurrent Diabetes Mellitus.

Adverse Reactions

*Note: not well documented in the rat

CNS:  possible balance disturbances associated with dizziness

CV:  possible arrhythmia

Resp:  possible nasal congestion

GI:  possible diarrhea

GU:  possible priapism (sustained erection in male rat)

Skin:  possible flushing

Dosage Recommendations

5 mg/kg, PO, q24hr 1,  41,  43, 44


  • Store tabs in a dry area away from heat. Refrigerate suspension or store at room temperature and dispose of any unused portion after 60 days.


Nathalie Baldwin, DVM

  1. Knafo S.E. (2014). Sildenafil citrate as a pulmonary protectant in chronic murine Mycoplasma pulmonis infection, Proceedings of AEMV (new ideas and procedures), Orlando: 6.
  2. Park, H.S., Park, J.W., Kim, H.J., Choi, C.W., Lee, H.J., Kim, B.I., & Chun, Y.S. (2013). Sildenafil alleviates bronchopulmonary dysplasia in neonatal rats by activating the hypoxia-inducible factor signaling pathway. American journal of respiratory cell and molecular biology, 48(1), 105–113.
  3. Plumb, D. (2008). Sildenafil Citrate. Plumb’s Veterinary Drug Handbook (6th ed., p. 820). Stockholm, Wis.: PharmaVet ;.
  4. Yen, C.H., Leu, S., Lin, Y.C., Kao, Y.H., Chang, L.T., Chua, S., Fu, M., Wu, C.J., Sun, C.K., & Yip, H.K. (2010). Sildenafil limits monocrotaline-induced pulmonary hypertension in rats through suppression of pulmonary vascular remodeling. Journal of cardiovascular pharmacology, 55(6), 574–584.
  5. C.Y. Ahn, S.K. Bae, S.H. Bae, H.E. Kang, S.H. Kim, M.G. Lee, and W.G. Shin. (2011). Pharmacokinetics of sildenafil and its metabolite, N-desmethylsildenafil, in rats with liver cirrhosis and diabetes mellitus, alone and in combination. Xenobiotica,41(2): 164–174.



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