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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

L-NAME abolished the effect of paricalcitol on improving endothelial dysfunction in 5/6 nephrectomized rats. SHAM and 5/6 NX rats were treated with vehicle or paricalcitol at 0.16 μg/kg as described in “Materials and Methods” (n = 9–11 per group). Aortic rings were preincubated with 100 μM L-NAME for 1 hour prior to the addition of PE to induce contraction, and the endothelium-dependent vasodilator acetylcholine was added in half-log increments (1 nM–30 μM) at 3–5 minute intervals. (a) Acetylcholine-evoked relaxation. (b) Serum PTH. (c) Serum Ca.
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fig5: L-NAME abolished the effect of paricalcitol on improving endothelial dysfunction in 5/6 nephrectomized rats. SHAM and 5/6 NX rats were treated with vehicle or paricalcitol at 0.16 μg/kg as described in “Materials and Methods” (n = 9–11 per group). Aortic rings were preincubated with 100 μM L-NAME for 1 hour prior to the addition of PE to induce contraction, and the endothelium-dependent vasodilator acetylcholine was added in half-log increments (1 nM–30 μM) at 3–5 minute intervals. (a) Acetylcholine-evoked relaxation. (b) Serum PTH. (c) Serum Ca.

Mentions: To further investigate how VDR activation improves endothelial function, we tested the effect of L-NAME. In this particular study, the maximal aorta relaxation response to acetylcholine in SHAM rats was −74.5 ± 3.6% with an EC50 of 157 nM. Relaxation was significantly reduced in uremic 5/6 NX vehicle-treated rats (−31.4 ± 4.7% with an EC50 of 358 nM). As shown in Figure 5(a), paricalcitol (0.16 μg/kg, i.p., 3x/weeks for two weeks) increased the maximal relaxation response to acetylcholine to −52.3 ± 9.6% (P <.05) with an EC50 at 368 nM. Addition of L-NAME at 100 μM during the aorta ring assay completely abolished the effect of paricalcitol on improving endothelial function. In this study, the serum PTH level was significantly reduced while the serum calcium level was not altered by paricalcitol (Figures 5(b) and 5(c)).


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)

L-NAME abolished the effect of paricalcitol on improving endothelial dysfunction in 5/6 nephrectomized rats. SHAM and 5/6 NX rats were treated with vehicle or paricalcitol at 0.16 μg/kg as described in “Materials and Methods” (n = 9–11 per group). Aortic rings were preincubated with 100 μM L-NAME for 1 hour prior to the addition of PE to induce contraction, and the endothelium-dependent vasodilator acetylcholine was added in half-log increments (1 nM–30 μM) at 3–5 minute intervals. (a) Acetylcholine-evoked relaxation. (b) Serum PTH. (c) Serum Ca.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: L-NAME abolished the effect of paricalcitol on improving endothelial dysfunction in 5/6 nephrectomized rats. SHAM and 5/6 NX rats were treated with vehicle or paricalcitol at 0.16 μg/kg as described in “Materials and Methods” (n = 9–11 per group). Aortic rings were preincubated with 100 μM L-NAME for 1 hour prior to the addition of PE to induce contraction, and the endothelium-dependent vasodilator acetylcholine was added in half-log increments (1 nM–30 μM) at 3–5 minute intervals. (a) Acetylcholine-evoked relaxation. (b) Serum PTH. (c) Serum Ca.
Mentions: To further investigate how VDR activation improves endothelial function, we tested the effect of L-NAME. In this particular study, the maximal aorta relaxation response to acetylcholine in SHAM rats was −74.5 ± 3.6% with an EC50 of 157 nM. Relaxation was significantly reduced in uremic 5/6 NX vehicle-treated rats (−31.4 ± 4.7% with an EC50 of 358 nM). As shown in Figure 5(a), paricalcitol (0.16 μg/kg, i.p., 3x/weeks for two weeks) increased the maximal relaxation response to acetylcholine to −52.3 ± 9.6% (P <.05) with an EC50 at 368 nM. Addition of L-NAME at 100 μM during the aorta ring assay completely abolished the effect of paricalcitol on improving endothelial function. In this study, the serum PTH level was significantly reduced while the serum calcium level was not altered by paricalcitol (Figures 5(b) and 5(c)).

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