Afferent arteriolar response to arachidonic acid: involvement of
metabolic pathways.
Imig, John D., and L. G. Navar.
Department of Physiology, Tulane University School of Medicine, New
Orleans, Louisiana
APStracts 3:0016F, 1996.
Arachidonic acid (AA) metabolites have been implicated in the control
of renal hemodynamics but the nature of the metabolites produced by
renal cells when AA is released has remained uncertain. Experiments
were performed using the in vitro perfused juxtamedullary nephron
preparation to examine the effects of perfusion and superfusion of AA
on the renal microvasculature. Extraluminal exposure of the vessels
by superfusion with solutions containing 0.1, 1.0, and 10 (M AA
decreased afferent arteriolar diameter by 8 2, 16 3, and 20 3%,
respectively. The same doses of AA added to the perfusate produced a
similar afferent arteriolar vasoconstriction. Inhibition of the major
enzymatic pathways unmasked differential responses of AA which were
dependent on the direction from which the vasculature was exposed to
AA. 17-ODYA (1 (M), an inhibitor of the cytochrome P450 pathway,
eliminated the vasoconstrictor response to superfused AA but had
little effect on the response to perfused AA. Lipoxygenase inhibition
with baicalein (0.5 (M) did not alter the afferent arteriolar
vasoconstriction during superfusion with AA but did attenuate the
vasoconstrictor response to perfused AA by 34%. Cyclooxygenase
inhibition with 10 (M indomethacin reduced the afferent arteriolar
response to superfusion with 10 (M AA by 46%; but the responses to
perfusion with AA were reversed leading to the unmasking of a 17%
afferent arteriolar dilation. The AA-induced vasorelaxation observed
during cyclooxygenase inhibition was prevented by the subsequent
addition of a P450 inhibitor. Additionally, after endothelial removal
with CHAPS, the vasodilatory response reverted to a vasoconstriction.
The results of this study demonstrate that in the rat, AA metabolites
exert predominant actions on afferent arterioles but differential
responses are mediated via different enzymatic pathways depending on
the origin of AA. Increased AA availability of intraluminal origin
leads to production of cyclooxygenase derived vasoconstrictor
metabolites and also to endothelial derived cytochrome P450
vasodilatory metabolites. In contrast, increased AA availability of
interstitial origin leads to production of vasoconstrictor cytochrome
P450 metabolites.
Received 5 July 1995; accepted in final form 16 January 1996.
APS Manuscript Number F213-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 January 96