scholarly journals Abnormal Regulation of Vitamin D Metabolism in Spontaneously Hypertensive Rats (SHR)

1987 ◽  
Vol 28 (4) ◽  
pp. 647-647 ◽  
Author(s):  
Yasuo Kimura ◽  
Takashi Shigematu ◽  
Yoshitaka Oda ◽  
Yoshindo Kawaguchi ◽  
Yo-suke Ogura ◽  
...  
1987 ◽  
Vol 253 (4) ◽  
pp. F712-F718
Author(s):  
C. H. Hsu ◽  
C. S. Yang ◽  
S. R. Patel ◽  
M. G. Stevens

We have studied the effect of dietary vitamin D restriction on serum levels of vitamin D metabolites in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Both WKY and SHR were fed a vitamin D-deficient or a vitamin D-supplemented diet beginning at 4 wk of age. In vitamin D-supplemented animals, the serum 1,25-dihydroxycholecalciferol [1,25(OH)2D3] concentration of WKY (55.4+/- 6.6 pg/ml, n = 5) was similar to the level of SHR (46.3+/- 5.9 pg/ml, n = 5). Plasma calcium concentration was not different between WKY and SHR. In animals fed a vitamin D-deficient diet, the serum concentration of 1,25-(OH)2D3 of SHR (23.0+/- 1.3 pg/ml, n = 5) was significantly lower than that of WKY (67.6+/- 4.6 pg/ml, n = 5, P less than 0.01). Plasma 25-hydroxycholecalciferol level was markedly decreased in both WKY (3.6+/- 0.5 ng/ml, n = 7) and SHR (2.8+/- 0.4 ng/ml). The SHR, but not the WKY, developed hypocalcemia (WKY, 9.68 mg/dl; SHR, 6.70 mg/dl). Despite hypocalcemia, fasting urinary Ca2+ excretion of SHR exceeded that of WKY. We conclude that the lower 1,25(OH)2D3 level in SHR fed a vitamin D-deficient diet may be due to a defect in the synthesis of 1,25(OH)2D3. The low level of 1,25(OH)2D3 is associated with renal wasting of calcium and hypocalcemia in SHR.


2020 ◽  
Vol 26 (1) ◽  
pp. 107-118 ◽  
Author(s):  
E. O. Bogdanova ◽  
O. N. Beresneva ◽  
O. V. Galkina ◽  
M. M. Parastaeva ◽  
I. M. Zubina ◽  
...  

Background. Even a moderate decrease in glomerular filtration rate leads to an increased risk of cardiovascular diseases (CVD), which is the leading cause of mortality in patients with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) underlies CVD development in renal dysfunction. The prevalence of LVH in patients with CKD stages 2–4 is 50–70 % and reaches 95 % at the beginning of dialysis, which significantly exceeds the number of cases in general population (15–21 %). Common hemodynamic factors associated with chronic kidney damage —hypertension (HTN), activation of the renin-angiotensin system, anemia, fluid and sodium retention, and others largely explain the high prevalence of LVH among patients with CKD. Nevertheless, the existence of additional non-hemodynamic mechanisms of myocardial remodeling (MR) is evident.Objective. To investigate the associations between the MR physiological/histological characteristics and laboratory parameters of calcium-phosphate metabolism in the initial stages of experimental CKD. Design and methods. Four groups of spontaneously hypertensive rats (SHR) were studied (n = 35): 3/4 nephrectomized rats (Nx) one month exposed after surgery (Nx(1), n = 9), 5/6 Nx two months after surgery (Nx(2), n = 8), sham operated rats one month after surgery (SO(1), n = 9) and two months after surgery (SO(2), n = 9). Myocardial mass index (MMI), systolic blood pressure (BP), proteinuria, creatinine (Cr) concentration, total calcium (Ca) and inorganic phosphate (Pi), 25-OH vitamin D (25OHD) and parathyroid hormone (PTH) in serum, myocardial morphology were studied in all experimental animals.Results. The models corresponded to the 1–3 stages CKD. There were no significant changes in serum total Ca (p = 0,066), Pi (p = 0,051) and PTH (p = 0,015) concentrations, the level of 25OHD was significantly lower in Nx(2) rats vs control (p = 0,015). MMI increased in all nephrectomized rats (p = 0,008). The cardiomyocytes (CM) thickness increased in Nx(1) and Nx(2) animals compared to the corresponding controls (p = 0,010, p = 0,002). A significant increase in interstitial (IF) and perivascular (PF) fibrosis occurred in Nx(2) rats with more damaging influence (p = 0,017, p = 0,004). CM thickness, IF and PF increased with the elevation of BP (r = 0,39, p = 0,038, r = 0,47, p = 0,026, r = 0,49, p = 0,031) and serum Cr (r = 0,68, p = 0,001, r = 0,61, p = 0,003, r = 0,69, p = 0,001), and the decrease in serum 25OHD concentration (r = –0,045, p = 0,047, r = –0,50, p = 0,020, r = –0,52, p = 0,012). Multiple linear regression analysis showed, that 25OHD is an independent predictor of myocardial fibrosis (IF: β = –0,38 ± 0,18, p = 0,047, PF: β = –0,34 ± 0,15, p = 0,032).Conclusions. The initial stages of CKD accompanied with HTN are associated with serum 25OHD concentration decrease CM hypertrophy and myocardial fibrosis. The CM growth is an earlier event in relation to the interstitial fibrosis. The obtained data suggest a possible role of vitamin D deficiency in the development of myocardial fibrotic lesions.


2019 ◽  
Vol 23 (6) ◽  
pp. 100-107
Author(s):  
E. O. Bogdanova ◽  
G. T. Ivanova ◽  
O. V. Galkina ◽  
I. M. Zubina ◽  
O. N. Beresneva ◽  
...  

INTRODUCTION. Vitamin D deficiency is commonly observed in patients with chronic kidney disease (CKD) due to decreased biosynthesis of 1,25(OH)2D3 in damaged renal tubules and increased catabolism of 1,25(OH)2D3 and 25OHD3. There is a growing evidence that vitamin D deficiency may contribute to impaired kidney function. Interventional studies have shown that vitamin D and its analogs attenuate the progression of renal fibrosis in experiment, and reduce proteinuria in patients with CKD. The renoprotective effects of vitamin D go far beyond its classical role in maintaining bone and mineral metabolism, which is a result of its pleiotropic action. THE AIM: to investigate the association between 25OH-hydroxyvitamin D (25OHD) level and renal fibrosis in spontaneously hypertensive rats (SHR) with early stages of experimental CKD.MATERIAL AND METHODS. Systolic blood pressure (BP), proteinuria, albuminuria, creatinine (Cr), urea (Ur), inorganic phosphate (Pi), 25OHD in serum were measured in nephrectomized (NE) and sham operated (SO) spontaneously hypertensive rats SHR (follow-up period 2, 4 and 6 months) and SO Wistar Kyoto rats (follow-up period 2 months), morphological light-optical study of kidney tissue was performed.RESULTS. The experimental model corresponded to the initial stages of CKD (Ur: 6.64 – 13.36 mmol/L). A significant increase in the area of renal fibrosis in animals with NE correlated with an increase in blood pressure (r = 0.51, p <0.001), serum Cr (r = 0.76, p <0.001), and albuminuria (r = 0.64, p <0.001) and proteinuria (r = 0.78, p <0.001) and a decrease in the concentration of 25OHD in serum (r = -0.67, p <0.001). In multiple regression analyzes, a reliable association of fibrosis with 25OHD was maintained (β = -0.28, p = 0.012). In addition, in ROC-analysis the largest value of the area under the curve was obtained for 25OHD (AUC = 0.95) to detect interstitial fibrosis more than 10 %.CONCLUSION. 25OHD depression at the initial stages of experimental CKD and hypertension is independently associated with the development of renal fibrosis.


1991 ◽  
Vol 260 (5) ◽  
pp. G691-G697 ◽  
Author(s):  
D. L. Cloney ◽  
R. W. Gray ◽  
M. E. Bruns ◽  
S. H. Burnett ◽  
M. L. Smith ◽  
...  

Intestinal Ca2+ malabsorption has been described in spontaneously hypertensive rats (SHRs), but the molecular basis for this defect is unknown. In this study, we measured intestinal alkaline phosphatase and vitamin D-dependent Ca(2+)-binding protein (calbindin-D9k), two proteins implicated in the active pathway of intestinal Ca2+ absorption. Both proteins were measured in the small intestines of SHRs and their normotensive controls, Wistar-Kyoto rats, before, during, and after development of hypertension (4, 9, 14, 18, and 28 wk of age). At all ages, alkaline phosphatase activity in duodenum (0-6 cm) was decreased by 30-57% (P less than 0.001) and by 47-75% in the 2nd intestinal segment (6-12 cm) (P less than 0.001-0.05). Calbindin-D9k was decreased similarly. The decreases of calbindin were statistically significant (P less than 0.001-0.05) in the duodena at 4, 14, 18, and 28 wk (9-30% decreases) and in the 2nd segment at 4, 14, and 18 wk (38-69% decreases; P less than 0.001-0.005). Decreased calbindin in SHRs was documented in animals from two suppliers. The deficiencies of calbindin-D9k and alkaline phosphatase could not be attributed to malnutrition or to a generalized brush-border defect as indicated by body weights and the intestinal marker enzyme sucrase. Although calbindin-D9k was decreased in young SHRs, the serum 1,25-dihydroxycholecalciferol [1,25(OH)2D3] was increased by 59 and 129% in 4- and 9-wk-old SHRs (P less than 0.001), respectively; by contrast, serum 1,25(OH)2D3 was unchanged or decreased in older SHRs.(ABSTRACT TRUNCATED AT 250 WORDS)


Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Tsuneo Takenaka ◽  
Tsutomu Inoue ◽  
Yoichi Ohno ◽  
Takashi Miyazaki ◽  
Akira Nishiyama ◽  
...  

Vitamin D diminishes renin expression. In addition, we previously reported that vitamin D increased renal expression of klotho in rats with normal kidney function. In the present study, effects of vitamin D on renal injury was assessed in four groups of rats (n=6-8 for each group); uni-nephrectomized stroke-prone spontaneously hypertensive rats fed high salt (6%) diet as a control (C), those treated with irbesartan (100 mg/kg/day) (I), rats treated with calcitriol (30 ng/kg/day) (V), and rats treated with both irbesartan and calcitriol (I+V). Six weeks later, rats were killed with over-anesthesia, and harvested right kidney for analysis. As shown in table, systolic blood pressure (SBP) in C (p<0.05) was higher than I and I+V groups. While renal angiotensin II (AngII) concentration was lower in I and I+V groups than C, plasma AngII levels of I and V groups are higher and lower than C (p<0.05), respectively. In addition, urine albumin/creatinine ratio (Alb/Cr) was lower in I and I+V group than C, and 8-epi-prostaglandin F2α (PGF2α) excretion was reduced in V and I+V groups (p<0.05). Immunoblot analysis revealed that compared to C, renal klotho expression was preserved in V and I+V group (p<0.05). Creatinine clearance (Ccr) was elevated in I+V group than C. The present data indicate that irbesartan effectively decreases blood pressure with reductions in renal AngII and albuminuria. Our findings demonstrate that vitamin D enhances klotho expression, suppressing oxidative stress and albuminuria without substantial changes in renal AngII. The current results may provide evidence that renal renin-angiotensin system is regulated independently of circulating one.


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