Protective effect of nicotinamide and l -arginine against monocrotaline-induced pulmonary hypertension in rats: gender d
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ARTICLE
Protective effect of nicotinamide and l‑arginine against monocrotaline‑induced pulmonary hypertension in rats: gender dependence Katarzyna Sztormowska‑Achranowicz1 · Zbigniew Jankowski2 · Ivan Kocić1 Received: 10 February 2020 / Revised: 27 June 2020 / Accepted: 29 June 2020 © The Author(s) 2020
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 25 mmHg at rest and > 30 mmHg during exercise and increased pulmonary vascular resistance [4]. Interestingly, the pressure in the right atrium and cardiac output (CO) are one of the most important indicators predicting the survival rate of PAH patients. Currently, therapeutic recommendations for PAH are focused on the pulmonary vessels and do not consider simultaneous treatment of myocardium dysfunction [5]. In this context, the use of sex hormones, especially progesterone, nicotinamide and l-arginine is promising [6–8]. Nicotinamide is known to have many biological and therapeutic properties, including antioxidant, anti-inflammatory, and proapoptotic [7]. Studies suggest nicotinamide has a protective effect on acute lung damage caused by ischemia, endotoxin or oxidative stress [8]. Recently, studies have shown that nicotinamide can inhibit poly (ADP-ribose) polymerase (PARP), which in response to free radicals increases
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rapidly, causing a decrease in NAD + and ATP (metabolic homeostasis). The role of nicotinamide in PARP inhibition is important in vascular smooth muscle cells (inhibits spasm), in myocardial cells or cancer cells as it maintains an appropriate level of ATP [9]. In addition, nicotinamide has been shown to regulate myocardial SUR2A receptors by increasing cardiac resistance to an ischemia/reperfusion reaction [10]. l-Arginine is a nitric oxide (NO) donor. Some diseases, for example atherosclerosis, hypercholesterolemia or pulmonary hypertension significantly reduce the level of NO [11, 12]. Vascular endothelial cells use l-arginine as a NO precursor for physiological processes such as: inhibition of myocyte proliferation, vascular remodeling, reduction of va
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