DL0805-1, a novel Rho-kinase inhibitor, attenuates lung injury and vasculopathy in a rat model of monocrotaline-induced pulmonary hypertension.
Eur J Pharmacol
; 919: 174779, 2022 Mar 15.
Article
en En
| MEDLINE
| ID: mdl-35092757
ABSTRACT
Pulmonary hypertension (PH) is a severe chronic cardiopulmonary dysfunction characterized by impaired of pulmonary circulation. Current therapeutic drugs mainly act as vasodilators, leading to an unsatisfactory prognosis. The Rho/ROCK pathway plays an important role in the cardiovascular system. DL0805-1, a novel Rho kinase inhibitor, synthesized by our institute and showed a protective effect on lung tissues and reduced right ventricular systolic pressure in a hypertensive crisis rat model in our previous study. The present study aims to explore the efficacy of DL0805-1 on PH. The classical PH rat model induced by a single subcutaneous injection of monocrotaline was used to investigate the therapeutic effect of DL0805-1 on PH and the underlying mechanisms. The results showed that the high dose of DL0805-1 had a better effect on the survival rate and controlled right ventricular systolic pressure (RVSP) of PH rats than fasudil. DL0805-1 also exhibited a superior lung protective effect and significantly improved pulmonary vascular function compared with bosentan. Regarding molecular mechanisms, DL0805-1 inhibited the ROCK pathway in both pulmonary arteries and lung tissues. Taken together, DL0805-1 alleviated lung injury and vasculopathy in experimental PH rats. DL0805-1 has the potential to be developed as a candidate drug for the treatment of PH.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Arteria Pulmonar
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Vasodilatadores
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Inhibidores de Proteínas Quinasas
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Quinasas Asociadas a rho
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Hipertensión Pulmonar
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Indazoles
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Nitrilos
Límite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2022
Tipo del documento:
Article