AJP - Renal Physiology, Vol 271, Issue 1 87-F93, Copyright © 1996 by American Physiological Society

ARTICLES

Afferent arteriolar response to arachidonic acid: involvement of metabolic pathways

J. D. Imig and L. G. Navar
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.

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 microM 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 that were dependent on the direction from which the vasculature was exposed to AA. 17-Octadecynoic acid (1 microM), an inhibitor of the cytochrome P-450 pathway, eliminated the vasoconstrictor response to superfused AA but had little effect on the response to perfused AA. Lipoxygenase inhibition with baicalein (0.5 microM) 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 microM indomethacin reduced the afferent arteriolar response to superfusion with 10 microM 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 P-450 inhibitor. Additionally, after endothelial removal with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (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 P-450 vasodilatory metabolites. In contrast, increased AA availability of interstitial origin leads to production of vasoconstrictor cytochrome P-450 metabolites.

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