Tags

Type your tag names separated by a space and hit enter

A new ATP-sensitive potassium channel opener protects the kidney from hypertensive damage in spontaneously hypertensive rats.
J Pharmacol Exp Ther. 2005 Nov; 315(2):501-9.JP

Abstract

The effects of iptakalim, a new ATP-sensitive potassium channel opener, were studied in spontaneously hypertensive rats (SHR). Treatment of 12-week-old male SHR (six animals in each group) with iptakalim by gastric lavage at doses of 1, 3, or 9 mg/kg/day for 12 weeks resulted in a lowering of blood pressure. Iptakalim provided significant renoprotection to SHR rats as measured by decreased proteinuria and improved renal function. Histological evidence demonstrated that iptakalim could reverse renal vascular remodeling (of afferent arterioles, arcuate arteries, or interlobular arteries), and improve pathological changes of glomerular, renal interstitial, and glomerular filtration membranes. These effects were accompanied by the decreased circulation and intrarenal concentrations of endothelin 1 and transforming growth factor beta1 (TGF-beta1), and down-regulated overexpression of genes for ET-1, endothelin-converting enzyme 1, TGF-beta1, and the subunits of ATP-sensitive potassium channels (K(ATP)), Kir1.1 and Kir6.1, in the kidney during hypertension. Abnormal expression of matrix components [collagen IV, fibronectin, matrix metalloproteinase 9 (MMP-9) and MMP tissue inhibitor 1 (TIMP-1)] was also significantly reversed by iptakalim. Our results demonstrate that chronic treatment with iptakalim not only reduces blood pressure but also preserves renal structure and function in SHR. In addition to reducing blood pressure, the renoprotective of iptakalim may be involved in inhibiting the circulation and intrarenal concentrations of endothelin 1 and TGF-beta1, regulating the expression of K(ATP) genes and correcting MMP-9/TIMP-1 imbalance in renal tissue, which may result in reducing the accumulation of extracellular matrix molecules.

Authors+Show Affiliations

Department of Cardiovascular Pharmacology, Beijing Institute of Pharmacology and Toxicology, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16051697

Citation

Xue, Hao, et al. "A New ATP-sensitive Potassium Channel Opener Protects the Kidney From Hypertensive Damage in Spontaneously Hypertensive Rats." The Journal of Pharmacology and Experimental Therapeutics, vol. 315, no. 2, 2005, pp. 501-9.
Xue H, Zhang YL, Liu GS, et al. A new ATP-sensitive potassium channel opener protects the kidney from hypertensive damage in spontaneously hypertensive rats. J Pharmacol Exp Ther. 2005;315(2):501-9.
Xue, H., Zhang, Y. L., Liu, G. S., & Wang, H. (2005). A new ATP-sensitive potassium channel opener protects the kidney from hypertensive damage in spontaneously hypertensive rats. The Journal of Pharmacology and Experimental Therapeutics, 315(2), 501-9.
Xue H, et al. A New ATP-sensitive Potassium Channel Opener Protects the Kidney From Hypertensive Damage in Spontaneously Hypertensive Rats. J Pharmacol Exp Ther. 2005;315(2):501-9. PubMed PMID: 16051697.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A new ATP-sensitive potassium channel opener protects the kidney from hypertensive damage in spontaneously hypertensive rats. AU - Xue,Hao, AU - Zhang,Ying-Li, AU - Liu,Guo-Shu, AU - Wang,Hai, Y1 - 2005/07/28/ PY - 2005/7/30/pubmed PY - 2006/1/13/medline PY - 2005/7/30/entrez SP - 501 EP - 9 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 315 IS - 2 N2 - The effects of iptakalim, a new ATP-sensitive potassium channel opener, were studied in spontaneously hypertensive rats (SHR). Treatment of 12-week-old male SHR (six animals in each group) with iptakalim by gastric lavage at doses of 1, 3, or 9 mg/kg/day for 12 weeks resulted in a lowering of blood pressure. Iptakalim provided significant renoprotection to SHR rats as measured by decreased proteinuria and improved renal function. Histological evidence demonstrated that iptakalim could reverse renal vascular remodeling (of afferent arterioles, arcuate arteries, or interlobular arteries), and improve pathological changes of glomerular, renal interstitial, and glomerular filtration membranes. These effects were accompanied by the decreased circulation and intrarenal concentrations of endothelin 1 and transforming growth factor beta1 (TGF-beta1), and down-regulated overexpression of genes for ET-1, endothelin-converting enzyme 1, TGF-beta1, and the subunits of ATP-sensitive potassium channels (K(ATP)), Kir1.1 and Kir6.1, in the kidney during hypertension. Abnormal expression of matrix components [collagen IV, fibronectin, matrix metalloproteinase 9 (MMP-9) and MMP tissue inhibitor 1 (TIMP-1)] was also significantly reversed by iptakalim. Our results demonstrate that chronic treatment with iptakalim not only reduces blood pressure but also preserves renal structure and function in SHR. In addition to reducing blood pressure, the renoprotective of iptakalim may be involved in inhibiting the circulation and intrarenal concentrations of endothelin 1 and TGF-beta1, regulating the expression of K(ATP) genes and correcting MMP-9/TIMP-1 imbalance in renal tissue, which may result in reducing the accumulation of extracellular matrix molecules. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/16051697/A_new_ATP_sensitive_potassium_channel_opener_protects_the_kidney_from_hypertensive_damage_in_spontaneously_hypertensive_rats_ DB - PRIME DP - Unbound Medicine ER -