Epoxygenase metabolites contribute to nitric oxide-independent afferent arteriolar vasodilation in response to bradykinin.

Imig JD, Falck JR, Wei S, Capdevila JH
J Vasc Res. 2001 38 (3): 247-55

PMID: 11399897 · DOI:10.1159/000051053

In the kidney, epoxyeicosatrienoic acids (EETs) have been suggested to be endothelium-derived hyperpolarizing factors (EDHFs). The aim of the present study was to determine the contribution of EETs to the preglomerular vasodilation elicited by bradykinin. Sprague-Dawley rats were studied utilizing an in vitro perfused juxtamedullary nephron preparation. The afferent arteriolar diameter was determined and the diameter averaged 19 +/- 1 microm (n = 26) at a renal perfusion pressure of 100 mm Hg. Addition of 1, 10 and 100 nM bradykinin to the perfusate dose-dependently increased afferent arteriolar diameter by 5 +/- 1, 12 +/- 2 and 17 +/- 2%, respectively. The nitric oxide inhibitor N(omega)-nitro-L-arginine reduced bradykinin-induced afferent arteriolar vasodilation by 50%, and the diameter increased by 9 +/- 2% in response to 100 nM bradykinin. Epoxygenase inhibitors N-methylsulphonyl-6-(2-propargyloxyphenyl)hexanamide or miconazole greatly attenuated the nitric oxide-independent component of the vasodilation elicited by bradykinin. Cyclooxygenase (COX) inhibition attenuated the nitric oxide-independent vasodilation elicited by 1 nM bradykinin but did not significantly affect the vascular response to 100 nM bradykinin. Combined inhibition of nitric oxide, COX and epoxygenase pathways completely abolished bradykinin-mediated afferent arteriolar vasodilation. In additional studies, renal microvessels were isolated and incubated with bradykinin and samples were analyzed by NICI/GC/MS. Under control conditions, renal microvascular EET levels averaged 49 +/- 9 pg/mg/20 min (n = 7). In the presence of bradykinin, EET levels were significantly higher and averaged 81 +/- 11 pg/mg/20 min (n = 7). These data support the concept that EETs are EDHFs and contribute to the nitric oxide-independent afferent arteriolar vasodilation elicited by bradykinin.

Copyright 2001 S. Karger AG, Basel

MeSH Terms (23)

8,11,14-Eicosatrienoic Acid Amides Animals Arterioles Bradykinin Culture Techniques Cyclooxygenase Inhibitors Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 Enzyme System Enzyme Inhibitors Indomethacin Kidney Kinetics Male Microcirculation Nitric Oxide Nitroarginine Oxygenases Prostaglandin-Endoperoxide Synthases Rats Rats, Sprague-Dawley Renal Circulation Vasodilation

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