Protective effect of nicotinamide and l-arginine against monocrotaline-induced pulmonary hypertension in rats: gender dependence

Abstract

Abstract Background The purpose of this paper was to examine the effects of nicotinamide (ND) and l-arginine (l-ARG) on pulmonary vascular and heart changes induced by pulmonary hypertension in rats in a gender-dependent way. Methods Experiments were performed on male (M) and female (F) rats. PAH was induced via monocrotaline injection (sc, 60/kg B.W.) on day one of the 23-day observational period. After that, the animals were sacrificed, hearts removed and weighed and the papillary muscles isolated to measure force of contraction (Fc). Morphological changes of pulmonary vessels were also examined. Results Mixed diet supplementation with l-ARG + ND prevented highly significant right ventricle enlargement induced by PAH in both, male and female rats. Weight ratios between the right ventricle (RV) on one side and the left ventricle with septum on the other (LV + S) decreased from 0.46 ± 0.016 g to 0.29 ± 0.006 g in males and from 0.63 ± 0.03 g to 0.24 ± 0.008 g in females, n = 6, p < 0.001. Additionally, PAH increased basal contractility in female groups, and each of the diet allocations (l-ARG, ND, and mixed) were found to restore contractility to control values. All diet protocols in male and female restored decreased responsiveness of the myocardium to norepinephrine in hearts obtained from rats with PAH and prevented vascular changes observed in pulmonary hypertension (thickness of blood vessels and cell infiltration). Conclusion Our study suggests that l-arginine, nicotinamide or both play a positive role in right ventricle function or the process reducing pulmonary vascular remodeling especially in a gender-independent way.