Formation and actions of 20-hydroxyeicosatetraenoic acid in rat
renal arterioles.
Imig, John D., Ai-Ping Zou, Dave E. Stec, David R. Harder, John R.
Falck, and Richard J. Roman.
Department of Physiology and Cardiovascular Research Center,
Medical College of Wisconsin, Milwaukee, WI 53226, The Clement
Zablocki Medical Center, Milwaukee, WI 53295, Department of
Physiology, Tulane University School of Medicine, New Orleans, LA
70112, Department of Molecular Genetics, University of Texas
Southwestern Medical Center, Dallas TX
APStracts 2:0206R, 1995.
The present study examined whether preglomerular arterioles of the rat
produce 20-hydroxyeicosatetraenoic acid (20-HETE) and whether 20-HETE
are vasoactive on these vessels. Rat preglomerular arterioles
produced 20-HETE (4.8 - 1.0 pmol/min/mg, n=7), and to a lesser extent
14, 15- and 11, 12- DiHETEs, 6-keto PGF1[alpha] and PGE2 when
incubated with 14C-arachidonic acid. The results of immunoblotting
and reverse transcription-polymerase chain reaction experiments
indicate that these vessels express mRNA and protein for a P4504A2
enzyme. Using the rat juxtamedullary nephron microvascular
preparation perfused in vitro with a cell-free media, addition of 20
-HETE (1 nM to 1 [mu]M) to the bath reduced the diameter of proximal
and distal portions of the afferent arterioles. At a concentration of
1 [mu]M, the diameter of the proximal and distal portions of the
afferent arteriole fell by 14 - 1 and 16 - 3% after 20-HETE. The
response to 20-HETE (1 [mu]M) was not altered by blockade of
cyclooxygenase, lipoxygenase, and P450 pathways. Blockade of the
large conductance, Ca---activated, K- channel with TEA (1 mM) reduced
the diameter of afferent arterioles by 10% and blocked the
vasoconstrictor response to 20-HETE (1 [mu]M). These results indicate
that 20-HETE is an endogenous constrictor of preglomerular arterioles
and suggest a role for the P4504A2 enzyme in the regulation of renal
vascular tone.
Received 28 April 1995; accepted in final form 14 July 1995.
APS Manuscript Number R255-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.