PT  - JOURNAL ARTICLE
AU  - Hiroshi Yamasowa
AU  - Satoko Shimizu
AU  - Takao Inoue
AU  - Masanori Takaoka
AU  - Yasuo Matsumura
TI  - Endothelial Nitric Oxide Contributes to the Renal Protective Effects of Ischemic Preconditioning
AID  - 10.1124/jpet.104.074427
DP  - 2005 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 153--159
VI  - 312
IP  - 1
4099  - http://jpet.aspetjournals.org/content/312/1/153.short
4100  - http://jpet.aspetjournals.org/content/312/1/153.full
SO  - J Pharmacol Exp Ther2005 Jan 01; 312
AB  - We determined whether endothelial nitric oxide synthase (eNOS) plays an important role in the renal protective effect of ischemic preconditioning (IP) against the ischemia/reperfusion-induced acute renal failure (ARF) by using eNOS-deficient (eNOS-/-) and wild-type (eNOS+/+) mice. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. IP, which consists of three cycles of 2-min ischemia followed by 5-min reperfusion, was performed prior to 45-min ischemia. In eNOS+/+ mice, IP treatment markedly attenuated the ischemia/reperfusion-induced renal dysfunction and significantly improved histological renal damage such as tubular necrosis, proteinaceous casts in tubuli, and medullary congestion. Constitutive nitric oxide synthase activity in the kidney without IP was markedly decreased 6 h after reperfusion, but this decreased response was not observed in eNOS+/+ mice with IP treatment. The improvement of renal dysfunction in eNOS+/+ mice with IP treatment was abolished by pretreatment with NG-nitro-l-arginine, a nonselective NOS inhibitor, whereas aminoguanidine, an inducible NOS inhibitor, had no effect. Finally, no protective effects of IP on ischemia/reperfusion-induced renal dysfunction and histological damage were observed in eNOS-/- mice. These findings strongly support the view that eNOS-mediated NO production plays a pivotal role in the protective effect of IP on ischemia/reperfusion-induced ARF. The American Society for Pharmacology and Experimental Therapeutics