Renoprotective Effect of Pravastation in Salt-Loaded Dahl Salt-Sensitive Rats

Kido, Miki; Ando, Katsuyuki; Oba, Shigeyoshi; Fujita, Toshiro

doi:10.1291/hypres.28.1009

Cited by 24 publications

(19 citation statements)

References 42 publications

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“…Shoring up endogenous antioxidant defenses with the administration of an antioxidant, such as PDTC, N-acetylcysteine or probucol, 13,105,108,109,[128][129][130][131] represent other avenues. Agents that are active in modulating oxidative stress and influencing the transcription of genes, which promote the proinflammatory vascular phenotype, such as 3-hydroxy-3-methyglutaryl coenzyme A reductase 102,[132][133][134] and ligands to peroxisome proliferator-activated receptor-gamma and -alpha, 135-139 also prove to be cardio-and renoprotective. Selective inhibition of phosphodiesterase isoforms, which iterate cyclic nucleotide second messengers (cAMP and cGMP) to downregulate mitogen-and antigen-induced T-cell proliferation, Th-1-and Th-2-derived proinflammatory cytokines and adhesion molecule expression in these cells have also been reported to be cardioprotective.…”

Section: Cellular and Molecular Pathways Leading To Proinflammatory Cmentioning

confidence: 99%

From aldosteronism to oxidative stress: the role of excessive intracellular calcium accumulation

et al. 2010

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Inappropriately (relative to dietary Na + ) elevated plasma aldosterone concentrations (PAC), or aldosteronism, have been incriminated in both the appearance of the cardiometabolic syndrome (CMS) and its progressive nature. The deleterious dual consequences of elevated PAC and dietary Na + have been linked to several components of the CMS, including salt-sensitive hypertension. Moreover, their adverse consequences are considered to be synergistic, culminating in a pro-oxidant phenotype with oxidative injury involving the heart and systemic tissues, including peripheral blood mononuclear cells (PBMC). Our experimental studies in rats receiving aldosterone/salt treatment have identified a common pathogenic event that links aldosteronism to the induction of oxidative stress. Herein, we review these findings and the important role of excessive intracellular Ca 2+ accumulation (EICA), or intracellular Ca 2+ overloading, which occurs in the heart and PBMC, leading to, respectively, cardiomyocyte necrosis with a replacement fibrosis and an immunostimulatory state with consequent coronary vasculopathy. The origin of EICA is based on elevations in plasma parathyroid hormone, which are integral to the genesis of secondary hyperparathyroidism that accompanies aldosteronism and occurs in response to plasma-ionized hypocalcemia and hypomagnesemia whose appearance is the consequence of marked urinary and fecal excretory losses of Ca 2+ and Mg 2+ . In addition, we found intracellular Ca 2+ overloading to be intrinsically coupled to a dyshomeostasis of intracellular Zn 2+ , which together regulate the redox state of cardiac myocytes and mitochondria via the induction of oxidative stress and generation of antioxidant defenses, respectively. To validate our hypothesis, a series of site-directed, sequential pharmacological and/or nutriceutical interventions targeted along cellular-molecular cascades were carried out to either block downstream events leading to the pro-oxidant phenotype or to enhance antioxidant defenses. In each case, the interventions were found to be cardioprotective. These cumulative salutary responses raise the prospect that pharmacological agents and nutriceuticals capable of influencing extra-and intracellular Ca 2+ and Zn 2+ equilibrium could prevent adverse cardiac remodeling and thereby enhance the management of aldosteronism.

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Section: Cellular and Molecular Pathways Leading To Proinflammatory Cmentioning

confidence: 99%

From aldosteronism to oxidative stress: the role of excessive intracellular calcium accumulation

et al. 2010

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“…8 Actually, in our previous report, 9 we demonstrated enhanced cuff-induced neointimal proliferation associated with vascular ROS overproduction and adventitial upregulation of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase in mice with an intrinsic deficiency of antioxidant adrenomedullin. Interestingly, salt loading increased plasma and urinary markers of oxidative stress 10,11 and ROS production from the injured aorta 12 and kidney 11 in DS rats. Conversely, in our recent study, 13 potassium supplementation ameliorated cardiac dysfunction associated with inhibition of NADPH oxidase in salt-loaded DS rats.…”

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confidence: 94%

Protective Effect of Dietary Potassium Against Vascular Injury in Salt-Sensitive Hypertension

et al. 2008

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Abstract-Hypertensive cardiovascular damage is accelerated by salt loading but counteracted by dietary potassium supplementation. We suggested recently that antioxidant actions of potassium contribute to protection against salt-induced cardiac dysfunction. Therefore, we examined whether potassium supplementation ameliorated cuff-induced vascular injury in salt-sensitive hypertension via suppression of oxidative stress. Four-week-old Dahl salt-sensitive rats were fed a normal-salt (0.3% NaCl), high-salt (8% NaCl), or high-salt plus high-potassium (8% KCl) diet for 5 weeks, and some of the rats fed a high-salt diet were also given antioxidants. One week after the start of the treatments, a silicone cuff was implanted around the femoral artery. Examination revealed increased cuff-induced neointimal proliferation with adventitial macrophage infiltration in arteries from salt-loaded Dahl salt-sensitive rats compared with that in arteries from non-salt-loaded animals (intima/media ratio: 0.471Ϯ0.070 versus 0.302Ϯ0.037; PϽ0.05), associated with regional superoxide overproduction and reduced nicotinamide-adenine dinucleotide phosphate oxidase activation and mRNA overexpression. On the other hand, simultaneous potassium supplementation attenuated salt-induced neointimal hyperplasia (intima/media ratio: 0.205Ϯ0.012; PϽ0.001), adventitial macrophage infiltration, superoxide overproduction, and reduced nicotinamide-adenine dinucleotide phosphate oxidase activation and overexpression. Antioxidants, which decrease vascular oxidative stress, also reduced neointima formation induced by salt excess. In conclusion, high-potassium diets seems to have a protective effect against the development of vascular damage induced by salt loading mediated, at least in part, through suppression of the production of reactive oxygen species probably generated by reduced nicotinamide-adenine dinucleotide phosphate oxidase. Key Words: hypertension Ⅲ sodium Ⅲ potassium Ⅲ antioxidants Ⅲ arteries N umerous studies have demonstrated that excessive salt intake causes cardiovascular damage and that this was counteracted by potassium supplementation. 1 According to the earlier report, 2 salt loading reduced the survival rate of Dahl salt-sensitive (DS) rats, a model of salt-sensitive hypertension, whereas potassium supplementation alleviated this salt-induced premature mortality, independent of its hypotensive action. It has been speculated that this may be a result of the vasoprotective effect of potassium, because potassium supplementation has been shown to ameliorate vascular endothelial dysfunction in salt-loaded DS rats. 3 Also, Ma et al 4 clearly demonstrated that high-potassium intake inhibited neointimal formation in several vascular injury models, such as a balloon injury of rat carotid and swine coronary 5 arteries from animals without hypertension. Thus, dietary potassium may have vasoprotective mechanisms beyond the blood pressure (BP)-lowering effect. Although it has been shown in in vitro experiments that potassium inhibited migration 6 an...

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“…Previous studies suggest that statins have a beneficial effect on kidney function. Thus, in animal models, statins prevent the development of renal injury, reduce blood pressure (BP) and inflammation, and enhance renal perfusion [3,4]. In a hypertensive rat model, statins decreased systolic BP and plasma angiotensin II in rats fed on a high salt diet [5].…”

Section: Introductionmentioning

confidence: 99%

Glomerular filtration rate and blood pressure are unchanged by increased sodium intake in atorvastatin‐treated healthy men

Paulsen

Holst

Bech

et al. 2009

Scandinavian Journal of Clinical and Laboratory Investigation

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Renoprotective Effect of Pravastation in Salt-Loaded Dahl Salt-Sensitive Rats

Cited by 24 publications

References 42 publications

From aldosteronism to oxidative stress: the role of excessive intracellular calcium accumulation

From aldosteronism to oxidative stress: the role of excessive intracellular calcium accumulation

Protective Effect of Dietary Potassium Against Vascular Injury in Salt-Sensitive Hypertension

Glomerular filtration rate and blood pressure are unchanged by increased sodium intake in atorvastatin‐treated healthy men

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