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Smooth Muscle Research Group, Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada T2N 4N1
Submitted 28 March 2003 ; accepted in final form 30 April 2003
The determinants of bradykinin (BK)-induced afferent arteriolar
vasodilation were investigated in the in vitro perfused hydronephrotic rat
kidney. BK elicited a concentration-dependent vasodilation of afferent
arterioles that had been preconstricted with ANG II (0.1 nmol/l), but this
dilation was transient in character. Pretreatment with the nitric oxide
synthase inhibitor N
-nitro-L-arginine
methyl ester (100 µmol/l) and the cyclooxygenase inhibitor ibuprofen (10
µmol/l) did not prevent this dilation when tone was established by ANG II
but fully blocked the response when tone was established by elevated
extracellular KCl, which suggests roles for both NO and endothelium-derived
hyperpolarizing factor (EDHF). We had previously shown that the EDHF-like
response of the afferent arteriole evoked by ACh was fully abolished by a
combination of charybdotoxin (ChTX;10 nmol/l) and apamin (AP; 1 µmol/l).
However, in the current study, treatment with ChTX plus AP only reduced the
EDHF-like component of the BK response from 98 ± 5 to 53 ± 6%
dilation. Tetraethylammonium (TEA; 1 mmol/l), which had no effect on the
EDHF-induced vasodilation associated with ACh, reduced the EDHF-like response
to BK to 88 ± 3% dilation. However, the combination of TEA plus ChTX
plus AP abolished the response (0.3 ± 1% dilation). Similarly,
17-octadecynoic acid (17-ODYA) did not prevent the dilation when it was
administered alone (77 ± 9% dilation) but fully abolished the EDHF-like
response when added in combination with ChTX plus AP (-0.5 ± 4%
dilation). These findings suggest that BK acts via multiple EDHFs: one that is
similar to that evoked by ACh in that it is blocked by ChTX plus AP, and a
second that is blocked by either TEA or 17-ODYA. Our finding that a component
of the BK response is sensitive to TEA and 17-ODYA is consistent with previous
suggestions that the EDHF released by BK is an epoxyeicosatrienoic acid.
arteriole; endothelium-derived hyperpolarizing factor; acetylcholine; 17-octadecynoic; epoxyeicosatrienoic acids; tetraethylammonium; charybdotoxin; apamin; potassium channels
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