Benzenesulfonamide attenuates monocrotaline-induced pulmonary arterial hypertension in a rat model

In this study, we examined the effects of LASSBio-965 (N-[2-(3,4-dimethoxyphenyl) ethyl]-benzenesulfonamide), a compound designed as a simplified structure of a non-selective phosphodiesterase 4 inhibitor, on vascular smooth muscle in vitro as well as in a rat model of monocrotaline (MCT)-induced pulmonary arterial hypertension. LASSBio-965 (50 mg/kg) treatment caused a significant decrease in right systolic ventricular pressure (32.47±3.09 mmHg) compared to the MCT-vehicle group (51.88±3.23 mmHg; P<0.05) and in the ratio of right ventricular weight to left ventricular weight plus septum (0.42±0.03 g compared to 0.59±0.06 g, respectively; MCT-vehicle group; P<0.05). LASSBio-965 induced a concentration-dependent relaxation of rat aortic rings, which was decreased by mechanical removal of the endothelium. Milrinone, rolipram, and sildenafil reduced the maximum relaxation (100%) to 22.4±5.8, 69.5±5.6 and 80.1±10.7%, respectively (P<0.05). Maximum relaxation responses of aortic and pulmonary artery rings were decreased in the MCT-vehicle group (54.80±5.69 and 35.87±4.78, respectively) compared to the control (91.51±4.79 and 54.32±2.39, respectively) but improved with LASSBio-965 treatment (50 mg/kg; 88.43±4.54 and 59.36±4.83, respectively). These results indicate that LASSBio-965 can attenuate the pulmonary arterial hypertension in an animal model most likely through the nonselective inhibition of phosphodiesterases 3, 4, and 5.