Selective antagonism of the postsynaptic alpha(1)-adrenoceptor is protective against ischemic acute renal failure in rats.
We investigated the effects of prazosin, an alpha(1)-adrenoceptor antagonist, on the pathogenesis of ischemic acute renal failure in rats. Ischemic acute renal failure was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. An in vivo microdialysis study revealed that renal interstitial norepinephrine levels were increased with the ischemia/reperfusion (n=3). Renal function in vehicle-treated acute renal failure rats markedly decreased 1 day after reperfusion (n=6), compared with those in sham-operated control animals (n=6). Pre-ischemic treatment with prazosin (100 microg/kg, i.v.) markedly and significantly attenuated the ischemia/reperfusion-induced renal dysfunction (n=6). Histopathological examination of the kidney of vehicle-treated acute renal failure rats revealed severe renal damage, which was also significantly suppressed by pre-ischemic treatment with 100 microg/kg prazosin. The same dose of prazosin given after reperfusion failed to improve the ischemia/reperfusion-induced renal dysfunction (n=6), in contrast to cases of the pre-ischemic treatment with this agent. The administration of prazosin before ischemia did not influence the elevation of renal venous plasma norepinephrine levels (n=6), which were observed both immediately and 1 day after reperfusion. From these findings, we suggest that norepinephrine released excessively from the post-ischemic kidney is involved in the pathogenesis of ischemic acute renal failure, probably acting at the postsynaptic alpha(1)-adrenoceptors.
Fujii
Toshihide
T
Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Sugiura
Takahiro
T
Ohkita
Mamoru
M
Kobuchi
Shuhei
S
Takaoka
Masanori
M
Matsumura
Yasuo
Y
D058186:Acute Kidney Injury / Q000517:prevention & control*; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000818:Animals; D007511:Ischemia / Q000150:complications / Q000188:drug therapy*; D007668:Kidney / Q000098:blood supply* / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000032:analysis; D011224:Prazosin / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D009638:Norepinephrine; D011224:Prazosin