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Changes in plasma levels of asymmetric dimethylarginine, symmetric dimethylarginine, and arginine after a single dose of vardenafil in patients with pulmonary hypertension
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
Umea Univ, Umea Univ Hosp, Dept Pharmacol & Clin Neurosci, Umea, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, Uppsala, Sweden.;Uppsala Univ, Div Analyt Pharmaceut Chem, Dept Med Chem, SE-75185 Uppsala, Sweden..
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2015 (English)In: Vascular pharmacology, ISSN 1537-1891, E-ISSN 1879-3649, Vol. 73, 71-77 p.Article in journal (Refereed) Published
Abstract [en]

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 Cl.

Place, publisher, year, edition, pages
2015. Vol. 73, 71-77 p.
Keyword [en]
Pulmonary hypertension, Vardenafil, Hemodynamics, Dimethylarginines, Arginine
National Category
Cardiac and Cardiovascular Systems
URN: urn:nbn:se:uu:diva-265699DOI: 10.1016/j.vph.2015.04.010ISI: 000362056600011PubMedID: 25934511OAI: oai:DiVA.org:uu-265699DiVA: diva2:866627
Available from: 2015-11-03 Created: 2015-11-02 Last updated: 2015-11-03Bibliographically approved

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Wernroth, LisaWikström, Gerhard
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