期刊
LIFE SCIENCES
卷 77, 期 22, 页码 2743-2751出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2005.02.027
关键词
ATP-sensitive potassium channels; gene expression; hypertension; spontaneously hypertensive rats; iptakalim
ATP-sensitive potassium channels (K-ATP) are thought to be targets for antihypertensive drugs that are potassium channel openers. In this study, the expression of genes encoding the K-ATP subunits, SUR2, Kir6.1 and Kir6.2, was detected in tissues from Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and SHR undergoing long-term treatment with iptakalim, a novel antihypertensive drug that acts via K-ATP. The transcript levels for SUR2, Kir6.1 and Kir6.2 in the heart, aortic smooth muscle, and tail artery smooth muscle were determined by reverse transcription-polymerase chain reaction (RT-PCR). In general, Kir6.2 and SUR2 were more highly represented in all SHR tissues compared with those of WKY, and transcripts of Kir6.2 were significantly higher in tail artery smooth muscle from SHR. Following long-term treatment with iptakalim, mRNA levels of Kir6.2 and SUR2 were reduced significantly in all tissues compared with those of untreated SHR. Kir6.1 expression was not significantly different between SHR and WKY, and was unaffected by iptakalim treatment. These results indicate that the expression of the K-ATP subunits genes, SUR2 and Kir6.2, are closely associated with hypertensive pathological states, and the effect of iptakalim on K-ATP mRNA levels may explain, in part, the effects of iptakalim in reversing vascular and cardiac remodeling. Furthermore, changes in Kir6.2 mRNA levels suggest that Kir6.x, as well as SUR, is responsible for drug binding. (c) 2005 Elsevier Inc. All rights reserved.
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