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

Sztormowska-Achranowicz, Katarzyna; Jankowski, Zbigniew; Kocić, Ivan

doi:10.1007/s43440-020-00125-y

Cited by 8 publications

(11 citation statements)

References 37 publications

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“…The observed decrease in nicotinamide may be related to its higher use in the nicotinamide phosphoribosyltransferase reaction that promotes pulmonary vascular remodeling in the development of pulmonary arterial hypertension ( Chen et al, 2017 ), a common finding in chronic hypoxia ( Ottolenghi et al, 2020 ; Gassmann et al, 2021 ). As a matter of facts, either nicotinamide ( Sztormowska-Achranowicz et al, 2020 ) or niacin (or nicotinic acid; Jia et al, 2020 ) are being investigated as drugs to ameliorate progression of hypoxia-induced pulmonary hypertension.…”

Section: Discussionmentioning

confidence: 99%

Inside the Alterations of Circulating Metabolome in Antarctica: The Adaptation to Chronic Hypoxia

et al. 2022

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Although the human body may dynamically adapt to mild and brief oxygen shortages, there is a growing interest in understanding how the metabolic pathways are modified during sustained exposure to chronic hypoxia. Located at an equivalent altitude of approximately 3,800 m asl, the Concordia Station in Antarctica represents an opportunity to study the course of human adaption to mild hypoxia with reduced impact of potentially disturbing variables else than oxygen deprivation. We recruited seven healthy subjects who spent 10 months in the Concordia Station, and collected plasma samples at sea level before departure, and 90 days, 6 months, and 10 months during hypoxia. Samples were analyzed by untargeted liquid chromatography high resolution mass spectrometry to unravel how the non-polar and polar metabolomes are affected. Statistical analyses were performed by clustering the subjects into four groups according to the duration of hypoxia exposure. The non-polar metabolome revealed a modest decrease in the concentration of all the major lipid classes. By contrast, the polar metabolome showed marked alterations in several metabolic pathways, especially those related to amino acids metabolism, with a particular concern of arginine, glutamine, phenylalanine, tryptophan, and tyrosine. Remarkably, all the changes were evident since the first time point and remained unaffected by hypoxia duration (with the exception of a slight return of the non-polar metabolome after 6 months), highlighting a relative inability of the body to compensate them. Finally, we identified a few metabolic pathways that emerged as the main targets of chronic hypoxia.

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Section: Discussionmentioning

confidence: 99%

Inside the Alterations of Circulating Metabolome in Antarctica: The Adaptation to Chronic Hypoxia

et al. 2022

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“…On the other hand, as nitric oxide precursors, citrulline and arginine present a cardioprotective function . It has been demonstrated that plasma levels of arginine and citrulline dropped precipitously after congenital cardiac surgery, while citrulline and arginine supplementation played a protective role in PAH. , Furthermore, in patients with preserved ejection fraction heart failure, administration of arginine and citrulline contributed to an improvement in pulmonary vascular resistance as well as the right ventricular ejection fraction, thereby improving the right ventricular function . Collectively, the decreased level of these amino acids may be hallmarks of a dysregulated RV function in PAH.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Reprogramming of the Right Ventricle and Pulmonary Arteries in a Flow-Associated Pulmonary Arterial Hypertension Rat Model

Liu

Qin

et al. 2021

ACS Omega

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Pulmonary arterial hypertension (PAH) is a complex devastating disease relevant to remarkable metabolic dysregulation. Although various research studies on PAH from a metabolic perspective have been emerging, pathogenesis of PAH varies in different categories. Research on metabolic reprogramming in flow-associated PAH remains insufficient. An untargeted metabolomic profiling platform was used to evaluate the metabolic profile of pulmonary arteries (PAs) as well as the right ventricle (RV) in a flow-associated PAH rat model in the present work. A total of 79 PAs and 128 RV metabolites were significantly altered in PAH rats, among which 39 metabolites were assessed as shared dysregulated metabolites in PAs and the RV. Pathway analysis elucidated that, in PAs of PAH rats, pathways of phenylalanine, tyrosine, and tryptophan biosynthesis and linoleic acid metabolism were significantly altered, while in the RV, arginine biosynthesis and linoleic acid metabolism were altered dramatically. Further integrated analysis of shared dysregulated PA and RV metabolites demonstrated that the linoleic acid metabolism and the arachidonic acid (AA) metabolism were the key pathways involved in the pathogenesis of flow-associated PAH. Results obtained from the present work indicate that the PAH pathogenesis could be mediated by widespread metabolic reprogramming. In particular, the dysregulation of AA metabolism may considerably contribute to the development of high blood flow-associated PAH.

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“…Previous studies reveal that patients with pulmonary arterial hypertension had lower α-tocopherol nicotinate levels and, similarly, lower antioxidants levels . Nicotinamide played an active role in the process of right ventricular function or pulmonary vascular remodeling, so it can improve the changes of pulmonary vascular and cardiac function in rats with pulmonary hypertension . Alleviation of renal impairment through the pathway linked to nicotinamide N -methyltransferase (NNMT) expression contributed to control of the progression of hypertensive nephropathy .…”

Section: Discussionmentioning

confidence: 99%

“…77 Nicotinamide played an active role in the process of right ventricular function or pulmonary vascular remodeling, so it can improve the changes of pulmonary vascular and cardiac function in rats with pulmonary hypertension. 78 Alleviation of renal impairment through the pathway linked to nicotinamide N-methyltransferase (NNMT) expression contributed to control of the progression of hypertensive nephropathy. 79 Nicotinamide nucleotide transhydrogenase activity affected the redox balance of mitochondria and the development of hypertension in mice.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics of Artichoke Bud Extract in Spontaneously Hypertensive Rats

Wang

Jiang

Liu³

et al. 2021

ACS Omega

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Hypertension adversely affects the quality of life in humans across modern society. Studies have attributed increased reactive oxygen species production to the pathophysiology of hypertension. So far, a specific drug to control the disease perfectly has not been developed. However, artichoke, an edible vegetable, plays an essential role in treating many diseases due to its potent antioxidant activities. The objective of this study is to evaluate the effect of artichoke bud extract (ABE) on heart tissue metabolomics of hypertensive rats. Spontaneously hypertensive rats and Wistar–Kyoto (WKY) rats were divided into six groups, then exposed to different doses comprising ABE, Enalapril Maleate, or 1% carboxylmethyl cellulose for 4 weeks. Their blood pressures were recorded at 0, 2, 3, and 4 weeks after the start of the test period. Thereafter, all rats were anesthetized, and blood was collected from their cardiac apexes. Then, we measured the levels for 15 kinds of serum biochemical parameters. An established orthogonal partial least square-discriminant analysis model completed the metabolomic analysis. Hypertensive rats in the ABE group exhibited well-controlled blood pressure, relative to those in the model group. Specifically, artichoke significantly lowered serum levels for total protein (TP), albumin (ALB), and uric acid (UA) in the hypertensive rats. This effect involved the action of eight metabolites, including guanine, 1-methylnicotinamide, p-aminobenzoic acid, NAD, NADH, uridine 5′-monophosphate, adenosine monophosphate, and methylmalonic acid. Collectively, these findings suggest that ABE may play a role in affecting oxidative stress and purine, nicotinate, and nicotinamide metabolism.

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

Cited by 8 publications

References 37 publications

Inside the Alterations of Circulating Metabolome in Antarctica: The Adaptation to Chronic Hypoxia

Inside the Alterations of Circulating Metabolome in Antarctica: The Adaptation to Chronic Hypoxia

Metabolic Reprogramming of the Right Ventricle and Pulmonary Arteries in a Flow-Associated Pulmonary Arterial Hypertension Rat Model

Metabolomics of Artichoke Bud Extract in Spontaneously Hypertensive Rats

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