Key result
Ambrisentan treatment significantly decreased right ventricular systolic pressure (14.67 vs 32.40 mmHg, p<0.001) and improved pulmonary arteriole remodeling in a monocrotaline-induced pulmonary arterial hypertension rat model.
Why the study?
Elevated endothelin-1 and NOX4 are linked to pulmonary arterial hypertension, and the study aimed to evaluate the effects of the ERA antagonist ambrisentan in a monocrotaline-induced PAH rat model.
Does ambrisentan improve right ventricular pressure, pulmonary pathology, and protein expression of ET-1, ERA, eNOS, and NOX4 in a monocrotaline-induced pulmonary arterial hypertension rat model?
Does ambrisentan improve right ventricular pressure, pulmonary pathology, and protein expression of ET-1, ERA, eNOS, and NOX4 in a monocrotaline-induced pulmonary arterial hypertension rat model?
Absolute Event Rate: 14.67% vs 32.4%
p-value: p=<0.001
Low-dose ambrisentan effectively reduces right ventricular pressure and pulmonary arteriole remodeling while recovering ET-1, ERA, and eNOS expression in a rat model of pulmonary arterial hypertension.
Hypothesis-generating in a rat model; leaves open translation to human pulmonary arterial hypertension.
BACKGROUND AND OBJECTIVES: Elevated endothelin (ET)-1 level is strongly correlated with the pathogenesis of pulmonary arterial hypertension (PAH). Expression level of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 4 is increased in the PAH patients. Ambrisentan, a selective endothelin receptor A (ERA) antagonist, is widely used in PAH therapy. The current study was undertaken to evaluate the effects of ambrisentan treatment in the monocrotaline (MCT)-induced PAH rat model. METHODS: Rats were categorized into control group (C), monocrotaline group (M) and ambrisentan group (Am). The M and Am were subcutaneously injected 60 mg/kg MCT at day 0, and in Am, ambrisentan was orally administered the day after MCT injection for 4 weeks. The right ventricle (RV) pressure was measured and pathological changes of the lung tissues were observed by Victoria blue staining. Protein expressions of ET-1, ERA, endothelial nitric oxide synthase (eNOS) and NOX4 were confirmed by western blot analysis. RESULTS: Ambrisentan treatment resulted in a recovery of the body weight and RV/left ventricle+septum at week 4. The RV pressure was lowered at weeks 2 and 4 after ambrisentan administration. Medial wall thickening of pulmonary arterioles and the number of intra-acinar arteries were also attenuated by ambrisentan at week 4. Protein expression levels of ET-1 and eNOS were recovered at weeks 2 and 4, and ERA levels recovered at week 4. CONCLUSIONS: Ambrisentan administration resulted in the recovery of ET-1, ERA and eNOS protein expression levels in the PAH model. However, the expression level of NOX4 remained unaffected after ambrisentan treatment.
No takes yet. Share an insight, caveat, or question.
Lee et al. (2019) studied Monocrotaline-induced pulmonary arterial hypertension (n=36). Ambrisentan vs. Monocrotaline without ambrisentan was evaluated on Right ventricle (RV) pressure at week 4 (p=<0.001). Ambrisentan treatment significantly decreased right ventricular systolic pressure (14.67 vs 32.40 mmHg, p<0.001) and improved pulmonary arteriole remodeling in a monocrotaline-induced pulmonary arterial hypertension rat model.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: