12-Hydroxyeicosatetraenoic acid participates in angiotensin II afferent arteriolar vasoconstriction by activating L-type calcium channels

Journal of Lipid Research

Xueying Zhao¹  Edward W. Inscho²  John D. Imig³  Shih Shen Yiu³ 

[1] Department of Physiology, Medical College of Georgia, Augusta, GA 30912;Tulane University School of Medicine, New Orleans, LA 70112;Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912;

关键词: lipoxygenase;    cytosolic calcium;    microcirculation;    kidney;   

DOI  :  

来源: DOAJ

【 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.

【 授权许可】

Unknown