Acute Effects of Vardenafil on Pulmonary Artery Responsiveness in Pulmonary Hypertension

Abstract EN

Phosphodiesterase type-5 (PDE-5) inhibitors are novel and important options for the treatment of pulmonary arterial hypertension (PAH).

Therefore, we aimed to examine effects of vardenafil, a PDE-5 inhibitor, on the pulmonary arteries isolated from rats with monocrotaline- (MCT-) induced pulmonary hypertension.

MCT (60 mg/kg) or its vehicle was administered by a single intraperitoneal injection to 6-week-old male Sprague Dawley rats.

Rats were sacrificed 21 days after MCT injection, and the main pulmonary arteries were isolated and then mounted in 20 mL organ baths.

Concentration-response curves for vardenafil (10−10–10−5 M) were constructed in phenylephrine- (Phe-) precontracted rings.

PAH caused marked rightward shift in the curves to vardenafil whereas maximal responses were not affected.

Inhibition of NO synthase (L-NAME, 10−4 M) or guanylyl cyclase (ODQ, 10−5 M) caused similar attenuation in responses evoked by vardenafil.

Moreover, contraction responses induced by CaCl2 (3×10−5–3×10−2 M) were significantly reduced in concentration-dependent manner by vardenafil.

In conclusion, vardenafil induced pulmonary vasodilatation via inhibition of extracellular calcium entry in addition to NO-cGMP pathway activation.

These results provide evidence that impaired arterial relaxation in PAH can be prevented by vardenafil.

Thus, vardenafil represents a valuable therapeutic approach in PAH besides other PDE-5 inhibitors.