Ps-B04-6: Fibroblast Growth Factor 21 - A Potential New Treatment for Hypertension?

Abstract

Objective: The life expectancy in PAH is very less, and only symptomatic treatment is available. Patients with pulmonary hypertension are mostly diagnosed with co-existing vitamin D deficiency. In PAH, there is an increase in the level and expression of PDE 5 enzyme that results in increased degradation of cGMP but there is also a simultaneous decrease in the activation of cGMP due to a subsequent decrease in eNOS mediated nitric oxide synthesis. Thus, limiting the efficacy of sildenafil as monotherapy in the treatment of PAH. Furthermore, vitamin D deficiency is also associated with reduced expression of eNOS mediated NO synthesis, which further decreases cGMP synthesis thus increasing disease severity. Hence, this study was undertaken to study the combined effect of sildenafil and vitamin D therapy in monocrotaline-induced PAH in rats.Design and method: Rats were fed on a vitamin D deficient diet with exposure to filtered fluorescent light to induce vitamin D deficiency. PAH was induced by a single s.c. injection of MCT 50 mg/kg. Rats were divided into 6 groups: Control, MCT, MCT+Sildenafil, MCT+Vitamin D, MCT+Vitamin D+Sildenafil and MCT+L-NAME+Vitamin D+Sildenafil. Haemodynamic, echocardiographic, histopathological and biochemical parameters were analysed. The expression and level of eNOS was done using immunohistochemistry and western blot. Results:The effect of the vitamin D sildenafil combination group was significantly higher than the vitamin D and sildenafil treated alone groups. This protective effect of vitamin D sildenafil combination in PAH is attenuated when administered with L-NAME (20 mg/kg). Furthermore, the administration of MCT reduced the expression of eNOS, which was significantly reversed by the treatment with vitamin D sildenafil combination compared to vitamin D and sildenafil alone. Conclusion:The effect of vitamin D in the treatment of PAH is comparable to sildenafil alone and is further improved when given in combination with sildenafil. Moreover, if pulmonary hypertension is accompanied by vitamin D deficiency it results in increased disease severity of PAH. Thus, sildenafil when combined with vitamin D may exert a synergistic effect in amelioration of symptoms and disease severity in patients of pulmonary hypertension.