Vasoactivity of epoxyeicosatrienoic acids (EETs) in murine renal arcuate arteries

Abstract

EETs mediate adenosine-induced vasodilation in rat preglomerular microvessels (PGMV); 11, 12-EET is the candidate mediator of PGMV dilation. We report on the response of the mouse arcuate artery to EETs. Male C57BL/6J mice (age 9–12 weeks) were anaesthetized and their kidneys excised and hemisected. Arcuate arteries (85 to 100 μm) were microdissected (4°C), cannulated and pressurized to 80 mmHg. Vessels were superfused with oxygenated Krebs’ solution (at 37°C) containing L-NAME (200 μM) and indomethacin (10μM). Vessels were then preconstricted with phenylephrine (20nM) producing an internal diameter (i.d.) of 46±6 μm. EETs were added to the superfusate and the i.d. was monitored by a video dimension analyzer. The threshold concentration of 11, 12-EET that dilated the arcuate artery (Δ13±2 μm i.d.) was 10−8M. Maximum dilation, Δ29±5 μm i.d., was achieved by 10−6M 11, 12-EET. The 5,6-, 8,9- and 14,15-EETs were equipotent and were ca 50% less active than 11, 12-EET. The ability of 11, 12-EET to increase the i.d. of the arcuate artery was compromised after incubation of arteries with an inhibitor of adenylyl cyclase, SQ 22536, for 15 min. 11, 12-EET increased i.d. by 29±5 μm before and by 7±2 μm (baseline 34±9 μM) after SQ 22536. Thus, the arcuate artery of the mouse resembles that of the rat in terms of responsiveness to EETs. It will serve as a model to delineate the regulation of EET-dependent renal vascular mechanisms.