Vascular Biology – Hemodynamics – Hypertension
Kidney International (2003) 63, 987–993; doi:10.1046/j.1523-1755.2003.00810.x
Glomerular autacoids stimulated by bradykinin regulate efferent arteriole tone
Yilin Ren, Jeffrey L Garvin, John R Falck, Kishore V Renduchintala and Oscar A Carretero
Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit, Michigan; and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
Correspondence: Oscar A. Carretero, M.D., Division of Hypertension and Vascular Research, Henry Ford Hospital, 2799 West Grand Blvd., Detroit, MI 48202, USA E-mail: ocarret1@hfhs.org
Received 25 January 2002; Revised 16 August 2002; Accepted 11 October 2002.
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 
m (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 m). 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 m. 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 and 20-HEDE, bradykinin caused dilatation and this effect was completely blocked by MS-PPOH (1 m) (from 7.6 0.6 to 7.3 0.5 m).
Conclusions
We concluded that in response to bradykinin, the glomerulus releases COX metabolites (probably prostaglandins) that have a vasodilator effect. When COXs are inhibited, the vasoconstrictor 20-HETE released by the glomerulus is able to oppose the vasodilator effect of bradykinin. This vasodilator effect is mediated by EETs released by the glomerulus and/or the efferent arteriole and does not involve nitric oxide. The balance between these opposing effects of various eicosanoids controls efferent arteriole resistance downstream from the glomerulus.
Keywords:
glomerulus, efferent arteriole, cP450, COX
