Changes in plasma levels of asymmetric dimethylarginine, symmetric dimethylarginine, and arginine after a single dose of vardenafil in patients with pulmonary hypertension

Vascul Pharmacol. 2015 Oct:73:71-7. doi: 10.1016/j.vph.2015.04.010. Epub 2015 Apr 29.

Abstract

Objective: We investigated whether vardenafil, a phosphodiesterase-5 inhibitor, alters plasma levels of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and arginine.

Patients and methods: ADMA, SDMA, and arginine were measured (0-540 min) in 12 patients with pulmonary hypertension after a single oral dose of vardenafil. Invasive hemodynamic data were collected at baseline and after 60 min.

Results: A reduction in ADMA was observed at 30 and 45 min with a median change of -11.1% (P=0.021) and -12.5% (P=0.002). SDMA decreased with a median -5.3% change (P=0.032) at 45 min. An increase in arginine, median 40.3% (P=0.002), 45.0% (P=0.010), and 77.1% (P=0.008) was observed at 120, 300, and 540 min respectively. An increase in the arginine/ADMA ratio, median 11.7% (P=0.012), 32.5% (P=0.003), 26.5% (P=0.021), 33% (P=0.007), 48.5% (P=0.007), and 63.1% (P=0.008) was observed at 15, 45, 60, 120, 300, and 540 min respectively. There was a positive correlation between vardenafil exposure and the percent change in the arginine/ADMA ratio from baseline to 540 min (r=0.80; P=0.01). A correlation between baseline mean right atrial pressure (mRAP) and baseline ADMA (r=0.65; P=0.023), and baseline SDMA (r=0.61; P=0.035) was observed. A correlation between the baseline arginine/ADMA ratio and baseline cardiac output (CO) (r=0.59; P=0.045) and baseline cardiac index (CI) (r=0.61; P=0.036) was observed. Baseline arginine/ADMA ratio correlated with baseline mRAP (r=-0.79; P=0.002). A correlation between change (0-60 min) in CI and change in arginine (r=0.77; P=0.003) as well as change in the arginine/ADMA ratio (r=0.61; P=0.037) was observed.

Conclusions: Vardenafil induced changes in ADMA, SDMA, arginine, and the arginine/ADMA ratio in patients with PH. An increase in arginine and the arginine/ADMA ratio was associated with improvement in CI.

Keywords: Arginine; Arginine (PubChem CID: 6322); Asymmetric dimethylarginine (PubChem CID: 123831); Dimethylarginines; Hemodynamics; Pulmonary hypertension; Symmetric dimethylarginine (PubChem CID: 169148); Vardenafil; Vardenafil (INN) (PubChem CID: 110634).

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / administration & dosage*
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Atrial Function, Right / drug effects
  • Atrial Pressure / drug effects
  • Biomarkers / blood
  • Cardiac Output / drug effects
  • Female
  • Humans
  • Hypertension, Pulmonary / blood
  • Hypertension, Pulmonary / diagnosis
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / physiopathology
  • Male
  • Middle Aged
  • Phosphodiesterase 5 Inhibitors / administration & dosage*
  • Time Factors
  • Treatment Outcome
  • Vardenafil Dihydrochloride / administration & dosage*
  • Vasodilator Agents / administration & dosage*

Substances

  • Antihypertensive Agents
  • Biomarkers
  • Phosphodiesterase 5 Inhibitors
  • Vasodilator Agents
  • symmetric dimethylarginine
  • Vardenafil Dihydrochloride
  • N,N-dimethylarginine
  • Arginine