Vascular Ca overload produced by vitamin D3 plus nicotine diminishes arterial distensibility in rats

Atkinson, Jeffrey; Poitevin, Pierre; Chillon, Jean‐Marc; Lartaud, Isabelle; Levy, B. I.

doi:10.1152/ajpheart.1994.266.2.h540

Cited by 30 publications

(38 citation statements)

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“…Vitamin D intoxication or pharmacologic doses of active vitamin D are associated with increased microvascular resistance and AC (31). Pharmacologic doses usually are applied in experimental studies, and vitamin D is associated with other substances, such as nicotine or antivitamin K, which potentiate its toxic effects (31).…”

Section: Discussionmentioning

confidence: 99%

“…Pharmacologic doses usually are applied in experimental studies, and vitamin D is associated with other substances, such as nicotine or antivitamin K, which potentiate its toxic effects (31). However, AC could be linked to hypercalcemia and not only to the action of vitamin D. In the general population, the circulating 1,25(OH) 2 D 3 levels were not or were inversely correlated with coronary calcifications (32).…”

Section: Discussionmentioning

confidence: 99%

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Mineral Metabolism and Arterial Functions in End-Stage Renal Disease

London¹,

Guérin²,

Verbeke

et al. 2007

Journal of the American Society of Nephrology

384

268

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, and the results of epidemiologic and clinical studies showed that large artery damage is a major factor that contributes to the mortality of these patients (2,3). The arterial system has two distinct, interrelated functions: To deliver an adequate blood supply from the heart to peripheral tissues (i.e., the conduit function) and to dampen blood flow and pressure oscillations that are caused by intermittent ventricular ejection (i.e., the cushioning function). Conduit function depends primarily on the diameter of the arterial lumen. It is highly efficient, and its physiologic adaptability is mediated through acute arterial diameter changes, which depend in large part on the endothelium response to alterations of shear stress, a phenomenon called flow-mediated dilation (FMD) (4). Conduit function disorders result from the narrowing of the arterial lumen or the diminished ability of the artery to dilate in response to shear stress changes. The cushioning function is altered by diminished distensibility that is caused by stiffening of arterial walls. Arterial stiffening results from fibroelastic intima thickening, increased collagen accumulation, and fragmentation of elastic lamellae with secondary fibrosis and calcification of the media (5).In patients with ESRD, both aspects of arterial functions are abnormal, characterized by arterial outward remodeling (6,7), increased arterial stiffening (6,7), and decreased FMD (8,9). These anomalies are enhanced further with aging, but these age-related effects are accelerated in uremic patients, in whom they are predictive of all-cause and cardiovascular mortality (3,10). The pathogenesis of these dysfunctions is not entirely clear. Conventional risk factors, such as aging and hypertension, only partly explain arterial abnormalities in patients with ESRD. Intimal and medial arterial calcifications (AC) are frequent in patients with ESRD (11); they result in arterial stiffening and abnormal conduit function and are associated with poor outcome (12). Several mineral metabolism disorders have been associated with increased AC and cardiovascular risk, including hyperphosphatemia, hyperparathyroidism, and increased calcium-phosphate product (13). Patients with chronic kidney disease and ESRD have vitamin D deficiency that is characterized by low serum 25-hydroxyvitamin D [25(OH)D 3 ] levels (14). With the decreased capacity of 1-␣-hydroxylase to synthesize calcitriol (1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]), the serum levels of the "hormonal" form of vitamin D also are low. Results of studies on the general population indicate that poor vitamin D status, characterized by low serum 25(OH)D 3 levels, is associated with higher prevalences of chronic heart failure, hypertension, and hyperparathyroidism (15-18), all fre-

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mineral Metabolism and Arterial Functions in End-Stage Renal Disease

London¹,

Guérin²,

Verbeke

et al. 2007

Journal of the American Society of Nephrology

384

268

View full text Add to dashboard Cite

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“…The inconsistency between the results of previous studies and our results were presumably because of using different animal models for in vivo studies. VDN treatment reportedly results in an approximately 15-fold increase in arterial Ca levels in young male Wistar rats 8 wk of age (18)(19)(20)(21), whereas this treatment results in ,10-fold increase in arterial Ca levels in young male SD rats of various ages (22)(23)(24). In female rats, the investigation of the calcification paradox by means of OVX plus VDN treatment in vivo has not been studied, except in our previous studies with SD rats of 6 wk (7,25).…”

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confidence: 99%

The Impact of Different Amounts of Calcium Intake on Bone Mass and Arterial Calcification in Ovariectomized Rats

Agata

Park

Hattori

et al. 2015

J Nutr Sci Vitaminol

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SummaryReduced estrogen secretion and low calcium (Ca) intake are risk factors for bone loss and arterial calcification in female rodents. To evaluate the effects of Ca intake at different amounts on bone mass changes and arterial calcification, 8-wk-old female Wistar rats were randomly placed in ovariectomized (OVX) control and OVX with vitamin D3 plus nicotine (VDN) treatment groups. The OVX with VDN rats were then divided into six groups to receive different amounts of Ca in their diets: 0.01%, 0.1%, 0.3%, 0.6%, 1.2%, or 2.4% Ca. After 8 wk of administration, low Ca intake groups with 0.01% and 0.1% Ca diets had significantly reduced bone mineral density (BMD) and bone mechanical properties as compared with those of the other groups, whereas high Ca intake groups with 1.2% and 2.4% Ca diets showed no differences as compared with the 0.6% Ca intake group. For both the 0.01% and 2.4% Ca intake groups, Ca levels in their thoracic arteries were significantly higher as compared with those of the 0.6% Ca diet group, and that was highly correlated with serum PTH levels. An increase in relative BMP-2 mRNA expression in the arterial tissues of the 0.01% and 2.4% Ca diet groups was also observed. These results suggested that extremely low Ca intake during periods of estrogen deficiency may be a possible risk for the complications of reduced BMD and arterial calcification and that extremely high Ca intake may promote arterial calcification with no changes in BMD.

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“…Only one high dose of vitamin D 3 (ϩ2 of nicotine) is required to induce, 2-6 days later, aortic wall calcification followed by aortic wall stiffening then hyperpulsatility (19,20,25,42). The latter remains elevated for Ͼ1 yr (2). Given the long half-life of vitamin D 3 (16 h in rats; Ref.…”

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confidence: 99%

“…23) and the fact that high doses of vitamin D 3 initially decrease renal blood flow by constricting the renal vasculature (36), we cannot exclude an initial phase of renal failure in VDN rats as a result of vitamin D toxicity. To avoid this initial phase of vitamin D toxicity, experiments on renal function have been performed in the present study 3 mo after VDN treatment, when hyperpulsatilty is established (2,15,25,26,34,40). We evaluated increased central arterial pulse pressure and aortic wall calcification and stiffness.…”

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confidence: 99%

Renal function and structure in a rat model of arterial calcification and increased pulse pressure

Gaillard¹,

Jover²,

Casellas³

et al. 2008

American Journal of Physiology-Renal Physiology

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[vitamin D and nicotine (VDN) treatment], we evaluated the relative importance of tissue calcification and hyperpulsatility in the etiology of renal failure. VDN rats showed significant increases in aortic wall calcium content (50 times; 992 Ϯ 171 vs. control 19 Ϯ 1 mol/g dry wt) and pulse pressure (1.5 times; 61 Ϯ 4 vs. control 40 Ϯ 2 mmHg). Significant renal calcification (16 times; 124 Ϯ 27 vs. control 8.1 Ϯ 0.7 mol/g dry wt) occurred mainly within the media of the preglomerular vasculature and in the areas of interstitial fibrosis in VDN. Extensive renal damages (5 times; 26 Ϯ 5% of collapsed-atrophic or sclerotic glomeruli, or glomerular cysts vs. control 5.2 Ϯ 0.3%; 28 times; 61 Ϯ 12% areas of focal, cortical areas exhibiting interstitial fibrosis per section vs. control 2.2 Ϯ 0.6%) were observed histologically. The glomerular filtration rate significantly decreased (880 Ϯ 40 vs. control 1,058 Ϯ 44 l ⅐ min Ϫ1 ⅐ g kidney wt Ϫ1 ). Albuminuria increased six times (1.6 Ϯ 0.4 vs. control 0.27 Ϯ 0.04 mg/24 h). There were significant linear relationships between albuminuria and pulse pressure (r 2 ϭ 0.408; n ϭ 24) or renal calcium content (r 2 ϭ 0.328; n ϭ 24; P Ͻ 0.05) and between glomerular filtration rate and pulse pressure (r 2 ϭ 0.168; n ϭ 27). To our knowledge, this study provides the first evidence of links between both 1) hyperpulsatility and renal dysfunction, and 2) renal calcification and renal dysfunction. Given the increasing frequency of endstage renal disease, this model could prove useful for preclinical evaluation of drugs that prevent or attenuate hyperpulsatility and/or tissue calcification. pulse pressure; renal failure; albuminuria; renal histology IN PATIENTS SUFFERING from end stage renal disease (ESRD), there are strong links between chronic renal failure and tissue (renal) calcification (4, 6, 37, 38). The mechanisms responsible are complex, and work on this problem has concentrated so far on altered phosphocalcium metabolism. Calcification also occurs in other tissues such as the aorta in these patients (17,(27)(28)(29), and this leads to increased arterial pulse pressure (hyperpulsatility; Refs. 17,[27][28][29]. O'Rourke and Safar (35), after revisiting the work of Byrom, suggested that organs with low vascular resistance such as the kidney are susceptible to the damaging effect of increased central pulse pressure. An increase in pulse pressure is one the most frequent cardiovascular risk factors in ESRD (18,[27][28][29].We approached the problem therefore of whether hyperpulsatility in addition to renal calcification is involved in the etiology of human renal failure. We used a preclinical, animal model, where hypervitaminosis D [plus nicotine (VDN)] produces, 3 mo later, aortic wall calcification with increased pulse pressure (26,34,40).In the light of the above, we evaluated in the VDN rat model the relative importance of renal calcification and increased central pulse pressure in the etiology of renal failure. Only one high dose of vitamin D 3 (ϩ2 of nicotine) is required to indu...

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Vascular Ca overload produced by vitamin D3 plus nicotine diminishes arterial distensibility in rats

Cited by 30 publications

References 0 publications

Mineral Metabolism and Arterial Functions in End-Stage Renal Disease

Mineral Metabolism and Arterial Functions in End-Stage Renal Disease

The Impact of Different Amounts of Calcium Intake on Bone Mass and Arterial Calcification in Ovariectomized Rats

Renal function and structure in a rat model of arterial calcification and increased pulse pressure

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