Abstract | BACKGROUND AND OBJECTIVES: METHODS AND RESULTS: In rats with hyperuricemia induced by 2% oxonic acid and 0.1 mmol/l uric acid, iptakalim prevented increases in systolic blood pressure, reduced the impairment of endothelial vasodilator function, and attenuated renal dysfunction and pathological changes in glomerular and renal interstitial tissue at 0.5, 1.5, and 4.5 mg/kg orally daily for 4 weeks. Serum levels of nitric oxide and prostacyclin, and gene expression of endothelial nitric oxide synthase in the aortic and intrarenal tissue, were increased, whereas the serum levels of endothelin-1 and gene expression of endothelin-1 in aortic and intrarenal tissue were decreased. However, serum levels of angiotensin II and renin remained unchanged in the hyperuricemic rats treated with iptakalim. In cultured rat aortic endothelial cells, amelioration of endothelial dysfunction by iptakalim was suggested by inhibition of the overexpression of intercellular adhesive molecule-1, vascular cell adhesive molecule-1, and monocyte chemoattractant protein-1 mRNA induced by uric acid, and reversal of the inhibitory effects of uric acid on nitric oxide release in a concentration-dependent manner, which could be abolished by pretreatment with glibenclamide, an ATP-sensitive potassium channel blocker. Iptakalim ameliorated hyperuricemia in this rat model by decreasing renal damage through its antihypertensive and endothelial protective properties, and it had no direct effects on anabolism, catabolism and excretion of uric acid. CONCLUSION:
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Authors | Chao-Liang Long, Xiu-Chuan Qin, Zhi-Yuan Pan, Kai Chen, Yan-Fang Zhang, Wen-Yu Cui, Guo-Shu Liu, Hai Wang |
Journal | Journal of hypertension
(J Hypertens)
Vol. 26
Issue 12
Pg. 2326-38
(Dec 2008)
ISSN: 0263-6352 [Print] England |
PMID | 19008712
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiotensins
- Endothelin-1
- KATP Channels
- N-(1-methylethyl)-1,1,2-trimethylpropylamine
- Propylamines
- Angiotensin II
- Uric Acid
- Nitric Oxide
- 6-Ketoprostaglandin F1 alpha
- Oxonic Acid
- Xanthine Oxidase
- Urate Oxidase
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Topics |
- 6-Ketoprostaglandin F1 alpha
(metabolism)
- Angiotensin II
(metabolism)
- Angiotensins
- Animals
- Cells, Cultured
- Disease Models, Animal
- Endothelin-1
(metabolism)
- Endothelium, Vascular
(cytology, drug effects, metabolism)
- Hypertension
(drug therapy, metabolism, prevention & control)
- Hyperuricemia
(chemically induced, complications, metabolism)
- KATP Channels
(agonists, drug effects, metabolism)
- Kidney
(blood supply, pathology)
- Kidney Diseases
(drug therapy, metabolism, prevention & control)
- Male
- Nitric Oxide
(metabolism)
- Oxonic Acid
(metabolism)
- Propylamines
(pharmacology, therapeutic use)
- Rats
- Rats, Sprague-Dawley
- Urate Oxidase
(metabolism)
- Uric Acid
(metabolism)
- Xanthine Oxidase
(metabolism)
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