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- Title
Glomerular autacoids stimulated by bradykinin regulate efferent arteriole tone.
- Authors
Ren, Yilin; Garvin, Jeffrey L.; Falck, John R.; Renduchintala, Kishore V.; Carretero, Oscar A.
- Abstract
Glomerular autacoids stimulated by bradykinin regulate efferent arteriole tone. Background. We have shown that when efferent arterioles are perfused retrograde to avoid the influence of vasoactive autacoids released by the glomerulus, bradykinin causes dilatation via release of cytochrome P450 (cP450) metabolites, probably epoxyeicosatrienoic acids (EETs). Here we tested the hypothesis that the glomerulus releases cyclooxygenase (COX) and cP450 metabolites. These eicosanoids, acting as vasopressor and vasodepressor autacoids, control efferent arteriole resistance downstream from the glomerulus. Methods. Rabbit efferent arterioles were perfused orthograde through the glomerulus from the end of the afferent arteriole to determine whether bradykinin induces the release of glomerular autacoids that influence efferent arteriole resistance. Efferent arterioles were preconstricted with norepinephrine, and increasing doses of bradykinin were added to the perfusate in the presence or absence of COX and cP450 inhibitors. Results. When efferent arterioles were perfused orthograde through the glomerulus, bradykinin at 10 nmol/L caused significant and reproducible dilatation; diameter increased from 8.0 ± 0.5 to 12.6 ± 0.4 μm (P < 0.05). This effect was not modified by a nitric oxide synthase (NOS) inhibitor. In the presence of indomethacin, a COX inhibitor, bradykinin-induced dilatation was almost completely blocked (from 8.0 ± 0.5 to 9.3 ± 0.6 μm). This blockade was completely reversed by 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE), a specific antagonist of the vasoconstrictor cP450 metabolite 20-hydroxyeicosatetraenoic acid (20-HETE); diameter increased from 6.6 ± 0.7 to 13.2 ± 0.5 μm. To test the hypothesis that this dilatation was due to EETs, a specific inhibitor of EET synthesis, N -methylsulphonyl-6-(2-proparglyloxyphenyl)hexanamide (MS-PPOH), was added to the arteriolar perfusate. In the presence of indomethacin...
- Subjects
KIDNEY glomerulus; CYTOCHROME P-450; CYCLOOXYGENASES; VASODILATION
- Publication
Kidney International, 2003, Vol 63, Issue 3, p987
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2003.00810.x