Background: Pulmonary hypertension is associated with an increase in pulmonary vascular resistance leading to pulmonary vascular changes, right ventricular hypertrophy, and heart failure. Pulmonary hypertension can be induced in animal models similar to humans where the changes are comparable. Monocrotaline (MCT), an alkaloid derived from a toxic plant, can be used to induce pulmonary hypertension in animals. Sildenafil has been used to treat patients with pulmonary hypertension since it induces smooth muscle relaxation. Atrial natriuretic peptide (ANP) is a hormone secreted naturally from the atria of the heart. An increase in ANP in hypervolemia and hypertension is beneficial since it induces a significant decrease in blood volume, therefore, lowers blood pressure. Studies showed that atrial natriuretic peptide combined with sildenafil reduces pulmonary arterial hypertension significantly. Cardiac hypertrophy due to pulmonary hypertension increases expression of myosin heavy chain β in the right ventricle of the heart.
Aims: To explore the ability of sildenafil to alleviate PH induced by Monocrotaline (MCT) in rats and explore the ANP level before and after induction of PH, and the administration of sildenafil.
Methods: Sixty four male Wister rats, were divided randomly into 4 groups: Control A, (7 Rats). Group received MCT only (14 rats), at dose 60mg /kg body weight subcutaneously. Group C received a single injection of MCT subcutaneously at a dose of 60mg /kg for 3 weeks and then sildenafil at a dose of 50mg/kg/day from the beginning of the fourth week to the end of the sixth week (The reversal group) counted 23 rats. Group D received a single injection of MCT subcutaneously at a dose of 60mg /kg for 3 weeks at the same time sildenafil was given at a dose of 50mg/kg from day 1 to the end of day 21 (The prevention group) consisting of 20 rats.
Results: The survival rate of the prevention group was the highest compared to other groups. The results revealed that MCT- treated rats and the reversal group showed a significant increase in ANP levels compared to the control one. The prevention group rats showed a significant decrease in ANP levels compared to both the reversal and the MCT- treated group. Fulton index ratio shows a significant increase in MCT treated rats and the reversal group compared to the control group, also it has an increasingly significant level to the reversal group compared to the prevention group. The percent of β- myosin heavy chain (MHC) is decreased significantly in the reversal group compared to both the MCT treated group and the control group. Nitric oxide (NO) levels were increased significantly in the reversal group compared to both the MCT treated group and the control group.
Conclusion: Sildenafil significantly decreases ANP levels in rats treated with MCT, and it also decreases cardiac hypertrophy induced by MCT.
Deanship of Research - Jordan University of Science andTechnology
