The combined use of L-arginine and tetrahydrobiopterin improves hemodynamic parameters in a rat model of pulmonary hypertension

Pulmonary arterial hypertension (PAH) is a severe condition leading to right heart failure and death within 2-3 years after diagnosis. Endothelium-dependent nitric oxide (NO) - mediated vasodilatation is impaired in patients with PAH. Endothelial nitric oxide synthase (eNOS) and its co-factor tetrahydrobiopterin (BH4) convert L-arginine to L-citrulline and NO. The aim of this study was to investigate the effects of combination therapy with L-arginine and BH4 in a rat model of PAH.
PAH was induced by unilateral left pneumonectomy and injection of monocrotaline (60mg/kg) in ten adult male Sprague-Dawley rats (300-350g). 21 days after monocrotaline-injection rats were randomized into two treatment arms: combination of oral L-arginine (20mg/kg) and BH4 (300mg/kg) or water once daily for 14 days. Hemodynamic parameters such as systolic pulmonary pressure, diastolic pulmonary pressure and mean pulmonary pressure (mPAP) were continuously recorded using implantable telemetry systems (DSI Datascience).

Baseline mean mPAP was 67.2 ± 12.7 mmHg in the treatment group and 55.5 ± 15.8 mmHg in the control group (p= 0.131). While in the treatment group the mean decrease in mPAP was 23.6 ± 6.4 mmHg, in the placebo group a mean decrease of 3.9 ± 18.2 mmHg was encountered (p= 0.031).
The combination therapy of L-arginine and BH4 in a rat model of severe PAH improves hemodynamic parameters.

No relevant conflicts of interest declared.