12-Hydroxyeicosatetraenoic acid participates in angiotensin II afferent arteriolar vasoconstriction by activating L-type calcium channels. J Lipid Res 2003 Dec;44(12):2391-9
Date
09/03/2003Pubmed ID
12951362DOI
10.1194/jlr.M300183-JLR200Scopus ID
2-s2.0-0347093588 (requires institutional sign-in at Scopus site) 47 CitationsAbstract
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 microm 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 micromol/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.
Author List
Yiu SS, Zhao X, Inscho EW, Imig JDMESH terms used to index this publication - Major topics in bold
12-Hydroxy-5,8,10,14-eicosatetraenoic AcidAngiotensin II
Animals
Calcium Channels
Calcium Signaling
Ion Channel Gating
Kidney
Lipoxygenase
Male
Myocytes, Smooth Muscle
Prostaglandin-Endoperoxide Synthases
Rats
Rats, Sprague-Dawley
Vasoconstriction
