Nitric oxide synthesis inhibition promotes renal production of carbon monoxide.
We tested the hypothesis that the status of NO synthesis influences the renal heme-heme oxygenase system. Studies were conducted in untreated rats and rats treated with the NO synthesis inhibitor N(G)-nitro-L-arginine methyl ester for 2 days. Treated and untreated rats were contrasted in terms of renal expression of heme oxygenase-1 and -2, renal carbon monoxide (CO)-generating activity, and urinary CO concentration and excretion rate. Heme oxygenase-1 and -2 proteins were similarly expressed in the kidneys of untreated and treated rats. In contrast, the NADPH-dependent component of the CO-generating activity of renal homogenates incubated with heme (a measure of heme oxygenase activity) was higher (P<0.05) in kidneys from rats treated with the NO synthesis inhibitor relative to corresponding data in untreated rats (1015+/-95 versus 379+/-111 pmol CO/mg per hour). Similarly, relative to corresponding data in untreated rats, rats treated with the NO synthesis inhibitor displayed increased (P<0.05) urinary CO concentration (920+/-174 versus 2286+/-472 pmol/mL) and urinary CO excretion (4.7+/-0.4 versus 14.3+/-2.7 pmol/min). This study demonstrates that NO synthesis inhibition upregulates the urinary concentration and excretion rate of CO, and the HO-dependent generation of CO by renal homogenates, without affecting the expression of renal heme oxygenase isoforms. Our findings imply that endogenous NO is an inhibitory regulator of renal CO generation by HO.
Rodriguez
Francisca
F
Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA. francisca_rodrigues@nymc.edu
Lamon
Brian D
BD
Gong
Weiying
W
Kemp
Rowena
R
Nasjletti
Alberto
A
D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism* / Q000652:urine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D002248:Carbon Monoxide; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D019331:NG-Nitroarginine Methyl Ester