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Vitamin d receptor activation mitigates the impact of uremia on endothelial function in the 5/6 nephrectomized rats.

Wu-Wong JR, Noonan W, Nakane M, Brooks KA, Segreti JA, Polakowski JS, Cox B - Int J Endocrinol (2010)

Bottom Line: Parathyroid hormone (PTH) suppression alone did not improve endothelial function since cinacalcet suppressed PTH without affecting endothelial-dependent vasorelaxation.N-omega-nitro-L-arginine methyl ester completely abolished the effect of paricalcitol on improving endothelial function.These results demonstrate that VDR activation improves endothelial function in CKD.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL 60612-7230, USA.

ABSTRACT
Endothelial dysfunction increases cardiovascular disease risk in chronic kidney disease (CKD). This study investigates whether VDR activation affects endothelial function in CKD. The 5/6 nephrectomized (NX) rats with experimental chronic renal insufficiency were treated with or without paricalcitol, a VDR activator. Thoracic aortic rings were precontracted with phenylephrine and then treated with acetylcholine or sodium nitroprusside. Uremia significantly affected aortic relaxation (-50.0 +/- 7.4% in NX rats versus -96.2 +/- 5.3% in SHAM at 30 muM acetylcholine). The endothelial-dependent relaxation was improved to -58.2 +/- 6.0%, -77.5 +/- 7.3%, and -90.5 +/- 4.0% in NX rats treated with paricalcitol at 0.021, 0.042, and 0.083 mug/kg for two weeks, respectively, while paricalcitol at 0.042 mug/kg did not affect blood pressure and heart rate. Parathyroid hormone (PTH) suppression alone did not improve endothelial function since cinacalcet suppressed PTH without affecting endothelial-dependent vasorelaxation. N-omega-nitro-L-arginine methyl ester completely abolished the effect of paricalcitol on improving endothelial function. These results demonstrate that VDR activation improves endothelial function in CKD.

No MeSH data available.


Related in: MedlinePlus

The blood chemistry in 5/6 NX uremic rats before and after paricalcitol treatment. The experimental conditions were as described in Figure 1. On Days 0 and 13 (24 hours after the last drug treatment), blood samples were collected for the measurement of (a) serum creatinine, (b) BUN, (c) serum PTH, (d) serum Ca, (e) ionized Ca, and (f) serum Pi. Mean ± standard error was calculated for each group (n = 9–11). One way ANOVA Dunnett test with 95% confidence intervals of difference was performed for statistical comparisons (Figures 2(a) 										and 2(b)).
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fig2: The blood chemistry in 5/6 NX uremic rats before and after paricalcitol treatment. The experimental conditions were as described in Figure 1. On Days 0 and 13 (24 hours after the last drug treatment), blood samples were collected for the measurement of (a) serum creatinine, (b) BUN, (c) serum PTH, (d) serum Ca, (e) ionized Ca, and (f) serum Pi. Mean ± standard error was calculated for each group (n = 9–11). One way ANOVA Dunnett test with 95% confidence intervals of difference was performed for statistical comparisons (Figures 2(a) and 2(b)).

Mentions: As shown in Figures 2(a) and 2(b), the serum creatinine and BUN levels were significantly elevated in the 5/6 nephrectomized (NX) rats compared to SHAM rats, indicating a uniform disease state. Paricalcitol at the three tested doses had no significant effect on either creatinine or BUN (versus Day 0). Figure 2(c) shows that, as expected, paricalcitol effectively suppressed serum PTH in a dose-dependent manner (a reduction of 41.6 ± 7.2%, 41.6 ± 7.4% and 48.2 ± 8.3% at 0.021, 0.042 and 0.083 μg/kg, resp.). Total serum calcium (Ca), phosphorus (Pi), and ionized Ca (iCa) levels were not significantly different in the 5/6 NX rats versus SHAM. Paricalcitol significantly increased serum Ca and iCa at 0.042 and 0.083 μg/kg (Figures 2(d) and 2(e)). Paricalcitol at the three doses had no effect on the Pi levels (Figure 2(f)).


Vitamin d receptor activation mitigates the impact of uremia on endothelial function in the 5/6 nephrectomized rats.

Wu-Wong JR, Noonan W, Nakane M, Brooks KA, Segreti JA, Polakowski JS, Cox B - Int J Endocrinol (2010)

The blood chemistry in 5/6 NX uremic rats before and after paricalcitol treatment. The experimental conditions were as described in Figure 1. On Days 0 and 13 (24 hours after the last drug treatment), blood samples were collected for the measurement of (a) serum creatinine, (b) BUN, (c) serum PTH, (d) serum Ca, (e) ionized Ca, and (f) serum Pi. Mean ± standard error was calculated for each group (n = 9–11). One way ANOVA Dunnett test with 95% confidence intervals of difference was performed for statistical comparisons (Figures 2(a) 										and 2(b)).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2821638&req=5

fig2: The blood chemistry in 5/6 NX uremic rats before and after paricalcitol treatment. The experimental conditions were as described in Figure 1. On Days 0 and 13 (24 hours after the last drug treatment), blood samples were collected for the measurement of (a) serum creatinine, (b) BUN, (c) serum PTH, (d) serum Ca, (e) ionized Ca, and (f) serum Pi. Mean ± standard error was calculated for each group (n = 9–11). One way ANOVA Dunnett test with 95% confidence intervals of difference was performed for statistical comparisons (Figures 2(a) and 2(b)).
Mentions: As shown in Figures 2(a) and 2(b), the serum creatinine and BUN levels were significantly elevated in the 5/6 nephrectomized (NX) rats compared to SHAM rats, indicating a uniform disease state. Paricalcitol at the three tested doses had no significant effect on either creatinine or BUN (versus Day 0). Figure 2(c) shows that, as expected, paricalcitol effectively suppressed serum PTH in a dose-dependent manner (a reduction of 41.6 ± 7.2%, 41.6 ± 7.4% and 48.2 ± 8.3% at 0.021, 0.042 and 0.083 μg/kg, resp.). Total serum calcium (Ca), phosphorus (Pi), and ionized Ca (iCa) levels were not significantly different in the 5/6 NX rats versus SHAM. Paricalcitol significantly increased serum Ca and iCa at 0.042 and 0.083 μg/kg (Figures 2(d) and 2(e)). Paricalcitol at the three doses had no effect on the Pi levels (Figure 2(f)).

Bottom Line: Parathyroid hormone (PTH) suppression alone did not improve endothelial function since cinacalcet suppressed PTH without affecting endothelial-dependent vasorelaxation.N-omega-nitro-L-arginine methyl ester completely abolished the effect of paricalcitol on improving endothelial function.These results demonstrate that VDR activation improves endothelial function in CKD.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL 60612-7230, USA.

ABSTRACT
Endothelial dysfunction increases cardiovascular disease risk in chronic kidney disease (CKD). This study investigates whether VDR activation affects endothelial function in CKD. The 5/6 nephrectomized (NX) rats with experimental chronic renal insufficiency were treated with or without paricalcitol, a VDR activator. Thoracic aortic rings were precontracted with phenylephrine and then treated with acetylcholine or sodium nitroprusside. Uremia significantly affected aortic relaxation (-50.0 +/- 7.4% in NX rats versus -96.2 +/- 5.3% in SHAM at 30 muM acetylcholine). The endothelial-dependent relaxation was improved to -58.2 +/- 6.0%, -77.5 +/- 7.3%, and -90.5 +/- 4.0% in NX rats treated with paricalcitol at 0.021, 0.042, and 0.083 mug/kg for two weeks, respectively, while paricalcitol at 0.042 mug/kg did not affect blood pressure and heart rate. Parathyroid hormone (PTH) suppression alone did not improve endothelial function since cinacalcet suppressed PTH without affecting endothelial-dependent vasorelaxation. N-omega-nitro-L-arginine methyl ester completely abolished the effect of paricalcitol on improving endothelial function. These results demonstrate that VDR activation improves endothelial function in CKD.

No MeSH data available.


Related in: MedlinePlus