Superoxide scavenging effects of N-acetylcysteine and vitamin C in subjects with essential hypertension.
BACKGROUND
It is not known whether the beneficial effects of N-acetylcysteine (NAC) in conditions associated with increased oxidative stress are caused by direct superoxide scavenging. We therefore compared the acute superoxide scavenging efficacy of NAC against vitamin C (VITC) on impaired endothelium-dependent vasodilation in subjects with essential hypertension.


METHODS
In a cross-over randomized study, the effects of intra-arterial administration of either NAC (48 mg/min) or VITC (18 mg/min) were examined in 15 subjects with essential hypertension and in 15 normotensive control subjects. Both endothelium-dependent and endothelium-independent vasodilation were determined as forearm blood flow (FBF) response to the intra-arterial administration of acetylcholine (Ach) and sodium nitroprusside (NP) in doses of 12 and 48 mug/min and 3.2 and 12.8 mug/min, respectively.


RESULTS
Subjects with essential hypertension had impaired responses to both doses of Ach (Delta% FBF to higher dose of Ach: 325 +/- 146 in subjects with essential hypertension v 540 +/- 199 in control subjects; P = .02) and an impaired response to the higher dose of NP (330 +/- 108 v 500 +/- 199; P = .03). The intra-arterial administration of NAC had no effect on these responses (higher dose of Ach: 325 +/- 146 without v 338 +/- 112 with NAC, NS). In contrast, intra-arterial VITC improved both the response to Ach (320 +/- 132 without v 400 +/- 185 with VITC, P = .05) and to NP (383 +/- 162 v 447 +/- 170, P = .05).


CONCLUSIONS
We found that NAC showed no statistically significant effect on either endothelium-dependent or endothelium-independent vasodilation in hypertensive subjects, whereas VITC did. We conclude that NAC is therefore not an effective superoxide scavenger in vivo. Other, nonimmediate effects such as the generation of glutathione may explain the beneficial effects of NAC in conditions associated with oxidative stress.
Schneider
Markus P
MP
Department of Medicine IV/Nephrology, University of Erlangen-Nürnberg, Erlangen, Germany.
Delles
Christian
C
Schmidt
Bernhard M W
BM
Oehmer
Sebastian
S
Schwarz
Thomas K
TK
Schmieder
Roland E
RE
John
Stefan
S
D000109:Acetylcholine / Q000494:pharmacology; D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D001783:Blood Flow Velocity / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D005542:Forearm / Q000098:blood supply; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D013481:Superoxides / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D016166:Free Radical Scavengers; D014665:Vasodilator Agents; D013481:Superoxides; D009599:Nitroprusside; D000109:Acetylcholine; D001205:Ascorbic Acid; D000111:Acetylcysteine