NO and NOS isoforms in the development of apoptosis in renal ischemia/reperfusion.
Nitric oxide (NO) and the expression of endothelial (eNOS) and inducible (iNOS) isoforms of nitric oxide synthase (NOS) are recognized as important mediators of physiological and pathological processes of renal ischemia/reperfusion (I/R) injury, but little is known about their role in apoptosis. The ability of the eNOS/NO system to regulate the iNOS/NO system and thus promote apoptosis was assessed during experimental renal I/R. Renal caspase-3 activity and the number of TUNEL-positive cells increased with I/R, but decreased when NOS/NO systems were blocked with L-NIO (eNOS), 1400W (iNOS), and N-nitro-l-arginine methyl ester (L-NAME; a nonselective NOS inhibitor). I/R increased renal eNOS and iNOS expression as well as NO production. The NO increase was eNOS- and iNOS-dependent. Blockage of NOS/NO systems with L-NIO or L-NAME also resulted in a lower renal expression of iNOS and iNOS mRNA; in contrast, eNOS expression was not affected by iNOS-specific blockage. In conclusion, two pathways define the role of NOS/NO systems in the development of apoptosis during experimental renal I/R: a direct route, through eNOS overexpression and NO production, and an indirect route, through expression/activation of the iNOS/NO system, induced by eNOS.
Department of Experimental Pathology, IIBB-CSIC, IDIBAPS, Barcelona 08036, Spain.
Jose Luis
JL
Viñas
Anna
A
Sola
Meritxell
M
Genescà
Vicente
V
Alfaro
Felip
F
Pí
Georgina
G
Hotter
D000578:Amidines / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001596:Benzylamines / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D007150:Immunohistochemistry; D007191:Indazoles; D007668:Kidney / Q000201:enzymology; D007674:Kidney Diseases / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood*; D052247:Nitric Oxide Synthase Type II / Q000097:blood*; D052250:Nitric Oxide Synthase Type III / Q000097:blood*; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*
D000578:Amidines; D001596:Benzylamines; D007191:Indazoles; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; D009952:Ornithine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester