Preventive effect of sildenafil on right ventricular function in rats with monocrotaline-induced pulmonary arterial...

Area of Science:

• Cardiovascular Research
• Pharmacology
• Animal Models

Background:

• Pulmonary hypertension (PH) is a severe condition characterized by high blood pressure in the pulmonary arteries.
• Monocrotaline (MCT) is a known agent for inducing experimental PH in animal models.
• Evaluating preventive treatments for PH is crucial for developing therapeutic strategies.

Purpose of the Study:

• To assess the preventive efficacy of sildenafil on monocrotaline-induced pulmonary hypertension in a rat model.
• To investigate the impact of sildenafil on hemodynamic parameters and cardiac function in rats with PH.

Main Methods:

• Male Sprague-Dawley rats were administered monocrotaline (MCT) to induce PH.
• Sildenafil was administered orally to a subset of MCT-injected rats.
• Echocardiography and cardiac catheterization were used to measure right ventricular systolic pressure (RVSP) and assess cardiac function at multiple time points.

Main Results:

• Sildenafil treatment significantly reduced RVSP at 4 and 6 weeks post-MCT injection compared to untreated controls.
• Sildenafil improved interventricular septal curvature, indicating prevention of pressure overload-induced changes.
• Diastolic function, assessed by the ratio of early diastolic to atrial systolic velocity, was improved by sildenafil.
• Myocardial contraction, evaluated by tricuspid annular plane systolic excursion and velocity, was not significantly preserved by sildenafil.

Conclusions:

• Sildenafil demonstrates a preventive effect against MCT-induced pulmonary hypertension in rats.
• The primary mechanism involves reducing RVSP and improving right ventricular diastolic function through vasodilation.
• Sildenafil exhibits minimal positive inotropic effects on the myocardium in this model.