Effects of sildenafil on maternal hemodynamics and fetal growth in normal rat pregnancy

Am J Physiol Regul Integr Comp Physiol. 2010 Feb;298(2):R433-8. doi: 10.1152/ajpregu.00198.2009. Epub 2009 Dec 2.

Abstract

It has been suggested that the phosphodiesterase-5 (PDE5) inhibitor sildenafil may be useful in the treatment of hypertension during pregnancy. However, we have reported a selective increase in renal inner medullary PDE5 that participates in the sodium retention of pregnancy. Therefore, the purpose of this study was to determine whether oral sildenafil treatment impairs maternal plasma volume expansion and/or fetal growth during rat pregnancy. Rats received sildenafil (10 mg x kg(-1) x day(-1), 50 mg x kg(-1) x day(-1), or 90 mg x kg(-1) x day(-1)) or vehicle on days 4-20 of pregnancy. On days 14-19, rats were housed in metabolic cages for collection of urine and measurement of food and water intake. Terminal hemodynamic and fetal measurements were taken on day 20. None of the sildenafil doses lowered blood pressure, and although all doses increased plasma cGMP concentrations, only the highest dose increased aortic and inner medullary cGMP content. Sildenafil had no effect on maternal weight gain; however, the highest dose decreased both plasma volume and renal sodium retention. The pup number and size were similar among the groups. Therefore, these studies suggest that low doses of systemic sildenafil may be safe during pregnancy in the rat, but higher doses may interfere with the physiological sodium retention and volume expansion of pregnancy. The effects of systemic sildenafil on blood pressure and sodium retention during hypertension in human pregnancy remain to be examined.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Creatinine / blood
  • Creatinine / urine
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / physiology
  • Female
  • Fetal Development / drug effects*
  • Fetus / blood supply
  • Hematocrit
  • Hemodynamics / drug effects*
  • Phosphodiesterase 5 Inhibitors
  • Phosphodiesterase Inhibitors / pharmacology*
  • Piperazines / pharmacology*
  • Plasma Volume / drug effects
  • Pregnancy
  • Pregnancy, Animal / physiology*
  • Purines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Regional Blood Flow / physiology
  • Sildenafil Citrate
  • Sodium / metabolism
  • Sulfones / pharmacology*
  • Vasodilator Agents / pharmacology*

Substances

  • Phosphodiesterase 5 Inhibitors
  • Phosphodiesterase Inhibitors
  • Piperazines
  • Purines
  • Sulfones
  • Vasodilator Agents
  • Sodium
  • Creatinine
  • Sildenafil Citrate
  • Cyclic Nucleotide Phosphodiesterases, Type 5