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Assessment of Vascular Function in Patients With Chronic Kidney Disease
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Assessment of Vascular Function in Patients With Chronic Kidney Disease

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Role of nitric oxide-producing and -degrading pathways in coronary endothelial dysfunction in chronic kidney disease

Satoru Tatematsu1, Shu Wakino, Takeshi Kanda

  • 1Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

Journal of the American Society of Nephrology : JASN
|February 3, 2007
PubMed

Insights

Chronic kidney disease (CKD) accelerates cardiovascular events by impairing coronary artery endothelial function. This dysfunction, linked to reduced nitric oxide (NO) pathways and elevated asymmetric dimethylarginine (ADMA), can be improved with all-trans retinoic acid therapy.

Area of Science:

  • Cardiovascular Medicine
  • Nephrology
  • Endocrinology

Background:

  • Cardiovascular events are common in chronic kidney disease (CKD).
  • Endothelial dysfunction, linked to nitric oxide (NO) pathways and asymmetric dimethylarginine (ADMA), is implicated but not directly shown in coronary arteries in CKD.
  • Investigating coronary endothelial function in early-stage CKD is crucial for understanding cardiovascular risk.

Purpose of the Study:

  • To investigate coronary artery endothelial function in a canine model of CKD.
  • To explore the role of NO pathways, ADMA, and related enzyme expression in CKD-induced coronary dysfunction.
  • To evaluate the therapeutic potential of all-trans retinoic acid (ATRA) in restoring coronary function.

Main Methods:

  • CKD was induced in dogs via heminephrectomy (1/2Nx) or five-sixths nephrectomy (5/6Nx).
  • Coronary blood flow and arteriolar diameter responses to acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) were measured.
  • Plasma ADMA, nitrite/nitrate levels, and coronary artery mRNA expression of DDAH-II and eNOS were analyzed. ATRA treatment was administered for 4 weeks.

Main Results:

  • Renal ablation significantly reduced GFR and increased plasma ADMA levels.
  • Acetylcholine-induced vasodilation was blunted in CKD groups, while sodium nitroprusside response remained unchanged.
  • Plasma nitrite/nitrate decreased, and coronary DDAH-II and eNOS mRNA expression were downregulated in CKD. ATRA treatment improved vasodilation and restored eNOS expression.

Conclusions:

  • Coronary endothelial function is impaired early in the course of CKD.
  • This dysfunction is associated with downregulated eNOS and/or DDAH-II in coronary arteries.
  • Targeting NO pathways, potentially with agents like ATRA, may prevent coronary dysfunction in CKD patients.

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