Role of oxidative stress versus lipids in monocrotaline-induced pulmonary hypertension and right heart failure.
Physiol Rep
; 9(22): e15090, 2021 11.
Article
in En
| MEDLINE
| ID: mdl-34816616
ABSTRACT
Pulmonary hypertension (PH) is a global health issue with a prevalence of 10% in ages >65 years. Right heart failure (RHF) is the main cause of death in PH. We have previously shown that monocrotaline (MCT)-induced PH and RHF are due to an increase in oxidative stress. In this study, probucol (PROB), a strong antioxidant with a lipid-lowering property, versus lovastatin (LOV), a strong lipid-lowering drug with some antioxidant effects, were evaluated for their effects on the MCT-induced RHF. Rats were treated (I.P.) with PROB (10 mg/kg ×12) or LOV (4 mg/kg ×12), daily 6 days before and 6 days after a single MCT injection (60 mg/kg). Serial echocardiography was performed and at 4-week post-MCT, lung wet-to-dry weight, hemodynamics, RV glutathione peroxidase (GSHPx), superoxide dismutase (SOD), catalase, lipid peroxidation, and myocardial as well as plasma lipids were examined. MCT increased RV systolic and diastolic pressures, wall thickness, RV end diastolic diameter, mortality, and decreased ejection fraction as well as pulmonary artery acceleration time. These changes were mitigated by PROB while LOV had no effect. Furthermore, PROB prevented lipid peroxidation, lowered lipids, and increased GSHPx and SOD in RV myocardium. LOV did decrease the lipids but had no effect on antioxidants and lipid peroxidation. A reduction in oxidative stress and not the lipid-lowering effect of PROB may explain the prevention of MCT-induced PH, RHF, and mortality. Thus targeting of oxidative stress as an adjuvant therapy is suggested.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Probucol
/
Lovastatin
/
Lipid Peroxidation
/
Oxidative Stress
/
Heart
/
Heart Failure
/
Hypertension, Pulmonary
/
Anticholesteremic Agents
/
Myocardium
/
Antioxidants
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Physiol Rep
Year:
2021
Document type:
Article
Affiliation country:
United States