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 (50mg/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.
Programa de Pós-Graduação em Farmacologia e Química Medicinal, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. gsudo@farmaco.ufrj.br
Gisele
G
Zapata-Sudo
Luana Braga
LB
Pontes
Jaqueline Soares
JS
da Silva
Lídia Moreira
LM
Lima
Isabelle Karine da Costa
IK
Nunes
Eliezer Jesus
EJ
Barreiro
Roberto Takashi
RT
Sudo
D000818:Animals; D004195:Disease Models, Animal; D065627:Familial Primary Pulmonary Hypertension; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D016686:Monocrotaline / Q000633:toxicity*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D017725:Ventricular Pressure / Q000187:drug effects; D000096926:Benzenesulfonamides
D016686:Monocrotaline; D013449:Sulfonamides; D000096926:Benzenesulfonamides; C576762:(N-(2-(3,4-dimethoxyphenyl)ethyl)-benzenesulfonamide)