Differential effects of N-acetylcysteine, theophylline or bicarbonate on contrast-induced rat renal vasoconstriction.
BACKGROUND
Vasoconstriction and reactive oxygen species (ROS) accumulation following contrast media (CM) injection are the key factors triggering CM-induced nephropathy. We compared the effects of N-acetylcysteine (NAC), theophylline or sodium bicarbonate on intrarenal vasoconstriction and ROS generation in a rat model of CM-induced nephropathy.


METHODS
Following a 3-day dehydration, Sprague-Dawley rats received CM (Telebrix) or sham 'CM' injection of 0.9% saline. Part of them received NAC, theophylline or bicarbonate prior to CM. Medullar renal blood flow was estimated by laser Doppler. The animals were sacrificed 1, 15 or 30 min after the respective treatments, their kidneys allocated and intrarenal STAT-8 isoprostane, PGE(2) and NO assessed.


RESULTS
Vasoconstriction was significantly attenuated by NAC. Theophylline only mildly attenuated the perfusion drop at 15 min, and was ineffective following 30 min. Unlike theophylline or bicarbonate, NAC significantly augmented intrarenal PGE(2). NAC, theophylline but not bicarbonate, gradually increased intrarenal NO. In all experimental variables, CM-induced ROS accumulation, represented by STAT-8 isoprostane estimation, progressed undisturbed.


CONCLUSIONS
(1) CM-induced intrarenal vasoconstriction was efficiently prohibited by NAC but not bicarbonate or theophylline; (2) the vasodilatory effect of NAC was mediated via increased PGE(2) synthesis, and (3) ROS accumulation was a primary renal response to CM-induced injury, not affected by any pharmacologic manipulations.
Efrati
Shai
S
Research & Development Department, Assaf Harofeh Medical Center, Zerifin, Israel. efratishai@013.net
Berman
Sylvia
S
Ilgiyeav
Ilia
I
Siman-Tov
Yariv
Y
Averbukh
Zhan
Z
Weissgarten
Joshua
J
D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D003287:Contrast Media / Q000009:adverse effects; D015232:Dinoprostone / Q000096:biosynthesis; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism; D007483:Iothalamic Acid / Q000009:adverse effects / Q000031:analogs & derivatives; D028421:Isoprostanes / Q000096:biosynthesis; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008833:Microcirculation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D017693:Sodium Bicarbonate / Q000494:pharmacology* / Q000627:therapeutic use; D013806:Theophylline / Q000494:pharmacology* / Q000627:therapeutic use; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
D003287:Contrast Media; D016166:Free Radical Scavengers; D028421:Isoprostanes; D014665:Vasodilator Agents; D007483:Iothalamic Acid; D009569:Nitric Oxide; D017693:Sodium Bicarbonate; C002587:ioxitalamic acid; D013806:Theophylline; D015232:Dinoprostone; D000111:Acetylcysteine