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

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 mum 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 :L 5 nmol/l. The 12(S)-HETE (5 mumol/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.-Yiu, S. S., X. Zhao, E. W. Inscho, and J. D. Imig. 12-Hydroxyeicosatetraenoic acid participates in angiotensin II afferent arteriolar vasoconstriction by activating L-type calcium channels.