Contribution of 20-hete to the vasodilator actions of nitric oxide
in renal arteries.
Alonso-Galicia, Magdalena, Cheng-Wen Sun, John R. Falck, David R.
Harder and Richard J. Roman.
1Department of Physiology, Medical College of Wisconsin, Milwaukee,
Wisconsin, 53226 and 2 Department of Molecular Genetics, University
of Texas Southwestern Medical Center, Dallas, Texas, 75235
APStracts 5:0105F, 1998.
The present study examined the contribution of elevations in cGMP
versus inhibition of cytochrome P4504A enzymes and the production of
the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE) to the
vasodilator actions of NO in renal arterioles. The NO donor, sodium
nitroprusside (SNP) at 10-5, 10-4, and 10-3 M reduced the production
of 20-HETE in microsomes prepared from renal arterioles to 80_2,
43_5, and 7_1% of control, respectively (n=4). In other experiments,
the vasodilator response to SNP (10-7 to 10-3 M) was examined in rat
renal interlobular arteries (<90 mm id), preconstricted with
phenylephrine (1 mM) under control conditions and after blockade of
the cGMP and P4504A pathways. Inhibition of guanylyl cyclase with ODQ
(10 (M, n=6) or cGMP-dependent protein kinase with KT5823 (1 mM, n=5)
attenuated the vasodilator response to SNP by 26 and 30%,
respectively. In contrast, inhibition of the endogenous production of
20-HETE with a suicide-substrate, irreversible inhibitor (17
-octadecynoic acid, 1(M, n=5) or a selective, competitive inhibitor of
20-HETE formation (dibromo-dodecenyl-methylsulfimide, 25 mM, n=5)
markedly impaired the vasodilator response to SNP by 76 and 78%,
respectively. Similarly, when 20-HETE levels were fixed at 100 nM
(n=6), the response to SNP was attenuated by 73%. Blockade of both
pathways with ODQ and 17-ODYA completely abolished the response to
SNP (n=6). These results indicate that the vasodilator response to NO
is largely cGMP-independent and that inhibition of 20-HETE formation
contributes to the cGMP-independent effects of NO in the renal
microcirculation.
Received 5 December 1997; accepted in final form 27 May 1998.
APS Manuscript Number F383-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 16 June 1998