文章基本信息

标题：12-Hydroxyeicosatetraenoic acid participates in angiotensin II afferent arteriolar vasoconstriction by activating L-type calcium channels
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作者：Shih Shen Yiu ; Xueying Zhao ; Edward W. Inscho 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2003
卷号：44
期号：12
页码：2391-2399
DOI：10.1194/jlr.M300183-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：The lipoxygenase (LO) metabolite, 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], constricts renal vessels, contributes to the vascular response to angiotensin, and has been implicated in cardiovascular and renal diseases. The current studies were performed to determine if renal microvascular 12(S)-HETE production is stimulated by angiotensin and the contribution of L-type calcium channels to the vasoconstriction elicited by 12(S)-HETE. Angiotensin increased renal microvascular 12(S)-HETE production by 64%, whereas cyclooxygenase metabolite production was not altered. Renal microvessels also expressed platelet-type 12-LO and leukocyte-type 12-LO. In the juxtamedullary preparation, afferent arteriolar diameter averaged 21 ± 1 μm and 12(S)-HETE caused a graded decrease in vessel caliber. The afferent arteriolar response to 12(S)-HETE was abolished during L-type calcium channel inhibition. Renal microvascular smooth muscle cells were studied using fluorescence microscopy. Renal myocyte [Ca²⁺]_i averaged 93 ± 5 nmol/l. The 12(S)-HETE (5 μmol/l) increased myocyte [Ca²⁺]_i to a peak value of 340 ± 55 nmol/l. The peak [Ca²⁺]_i response following exposure to 12(S)-HETE was greatly attenuated in the absence of extracellular Ca²⁺ or calcium channel blockade. These results demonstrate that renal microvascular 12(S)-HETE production is increased in response to angiotensin, and activation of L-type calcium channels is an important mechanism responsible for the afferent arteriolar vasoconstriction elicited by 12(S)-HETE.