Impaired nitric oxide- and endothelium-derived hyperpolarizing factor-dependent dilation of renal afferent arteriole in Dahl salt-sensitive rats.
OBJECTIVE
We previously demonstrated that acetylcholine elicited nitric oxide-dependent sustained and endothelium-derived hyperpolarizing factor (EDHF)-dependent transient dilation of afferent arterioles. The present study examined whether free radicals interacted with nitric oxide-dependent and EDHF-dependent vasodilator mechanisms in renal microvessels of salt-sensitive hypertension, using the isolated perfused hydronephrotic kidney.


RESULTS
Following the pretreatment with indomethacin (100 micromol/L) with or without nitro- l-arginine methylester (100 micromol/L), the effect of acetylcholine on noradrenaline (0.3 micromol/L)-induced constriction was evaluated in kidneys from Dahl salt-sensitive and salt-resistant rats. Although acetylcholine (0.01-10 micromol/L) caused dose-dependent and sustained vasodilation of afferent arterioles, attenuated dilation was observed in Dahl salt-sensitive rats, compared with that in salt-resistant rats (58 +/- 4 vs 101 +/- 11% reversal at 10 micromol/L acetylcholine). In the presence of nitro- l-arginine methylester, acetylcholine elicited only transient dilation, with vasodilator response blunted in Dahl salt-sensitive rats (64 +/- 4 vs 100 +/- 9% reversal at 10 micromol/L acetylcholine). Furthermore, chronic (8-10 weeks) treatment with tempol caused partial restoration of acetylcholine (10 micromol/L)-induced sustained arteriolar dilation (71 +/- 3% reversal), but complete reversal of transient dilation (92 +/- 4% reversal). Finally, acute treatment with tempol not only improved the sustained component of the acetylcholine-induced dilation but also restored the impaired responsiveness of transient dilation in Dahl salt-sensitive rats.


CONCLUSIONS
Both sustained (nitric oxide-mediated) and transient (EDHF-mediated) components of acetylcholine-induced afferent arteriolar dilation were attenuated in Dahl salt-sensitive rats, which was attributed, in part, to enhanced free radical activity. A reversal of the sustained and transient vasodilation by the acute tempol treatment suggests possible interaction between free radicals and EDHF as well as increased bioavailability of nitric oxide.
Ozawa
Yuri
Y
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Hayashi
Koichi
K
Kanda
Takeshi
T
Homma
Koichiro
K
Takamatsu
Ichiro
I
Tatematsu
Satoru
S
Yoshioka
Kyoko
K
Kumagai
Hiroo
H
Wakino
Shu
S
Saruta
Takao
T
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D001685:Biological Factors / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D020303:Rats, Inbred Dahl; D014664:Vasodilation / Q000187:drug effects
D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D000109:Acetylcholine