Mechanism involved in bradykinin-induced efferent arteriole dilation.
BACKGROUND
There is evidence that kinins play a role in the regulation of renal hemodynamics. The balance of vascular resistance in afferent and efferent arterioles (Af-Art and Ef-Art) is a crucial factor in controlling glomerular filtration. We have previously reported that bradykinin has a biphasic effect on the Af-Art and that dilation and constriction are due to cyclooxygenase products, not nitric oxide (NO). The present study was designed to examine (1) the direct effect of bradykinin on the Ef-Art and (2) the mechanisms that mediate bradykinin-induced Ef-Art dilation.


METHODS
Isolated Ef-Arts were microperfused retrograde while maintaining the Ef-Art pressure at 30 mm Hg. Isolated Ef-Arts were preconstricted with norepinephrine.


RESULTS
Perfusing the Ef-Art lumen with bradykinin caused dose-dependent vasodilation, increasing diameter from 6.9 +/- 0.7 to 8.0 +/- 0.8 (0.01 nmol/L), 8.3 +/- 0.7* (0.1 nmol/L), 10.3 +/- 0.7* (1 nmol/L) and 11.5 +/- 0.8* microm (10 nmol/L; N = 8; *P < 0.05 vs. NE). Neither L-NAME nor indomethacin blocked the vasodilator effect of bradykinin; the diameter increased from 8.1 +/- 0.9 to 12.9 +/- 0.6 microm (10 nmol/L; P < 0.05 vs. control; N = 6) in the L-NAME-treated group and from 7.4 +/- 0.9 to 11.0 +/- 1.0 microm (10 nmol/L; P < 0.05 vs. control; N = 6) in the indomethacin-treated group. However, 25 micromol/L 17-ODYA, a cytochrome cP450 inhibitor, blocked the vasodilator effect of 10-8 mol/L bradykinin, leaving diameter unchanged (from 7.9 +/- 0.8 to 7.7 +/- 0.7 microm; N = 6). Finally, 0.1 micromol/L icatibant, a B2 receptor antagonist, completely blocked the vasodilation induced by bradykinin, and the diameter went from 7.8 +/- 0.7 to 8.3 +/- 0.8 microm (10 nmol/L).


CONCLUSIONS
Bradykinin dilates Ef-Arts, but in contrast to Af-Arts its effect is not biphasic. The vasodilator effect of bradykinin in Ef-Arts via B2 receptors is mediated by cP450 metabolites (probably EETs), but not by NO or cyclooxygenase products.
Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit, Michigan 48202, USA.
YiLin
Y
Ren
Jeffrey
J
Garvin
Oscar A
OA
Carretero
D000818:Animals; D001160:Arterioles / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000098:blood supply*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D011817:Rabbits; D043782:Receptor, Bradykinin B2; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D065168:Bradykinin Receptor Antagonists; D016861:Cyclooxygenase Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D043782:Receptor, Bradykinin B2; D009569:Nitric Oxide; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester