L-arginine protects from ischemia-reperfusion-induced endothelial dysfunction in humans in vivo.
It has been shown that nitric oxide (NO) protects from myocardial ischemia-reperfusion injury in animal models. The present study investigated whether administration of the NO substrate l-arginine protects against ischemia-reperfusion-induced endothelial dysfunction in humans. Forearm blood flow was measured with venous occlusion plethysmography in 16 healthy male subjects who were investigated on two occasions. Forearm ischemia was induced for 20 min followed by 60-min reperfusion. With the use of a crossover protocol, the subject received a 15-min intrabrachial artery infusion of l-arginine (20 mg/min) and vehicle (saline, n = 12 or d-arginine, n = 4) starting at 15 min of ischemia on two separate occasions. Compared with preischemia, endothelium-dependent increase in forearm blood flow induced by intra-arterial acetylcholine (3-30 microg/min) was significantly impaired at 15 and 30 min of reperfusion when the subjects received saline (P < 0.001). When the subjects received l-arginine, the acetylcholine-induced increase in forearm blood flow was not significantly affected by ischemia-reperfusion. The recovery of endothelium-dependent vasodilatation at 15- and 30-min reperfusion was significantly greater after administration of l-arginine than after saline (P < 0.05). d-Arginine did not affect the response to acetylcholine. Endothelium-independent vasodilatation to nitroprusside was not affected during reperfusion. These results demonstrate that the NO substrate l-arginine significantly attenuates ischemia-reperfusion-induced endothelial dysfunction in humans in vivo. This suggests that l-arginine may be useful as a therapeutic agent in the treatment of ischemia-reperfusion injury in humans.
Pernow
John
J
Department of Cardiology, Karolinska Hospital, S-171 76 Stockholm, Sweden. john.pernow@ks.se
Bohm
Felix
F
Beltran
Emma
E
Gonon
Adrian
A
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001120:Arginine / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control*; D013237:Stereoisomerism; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009599:Nitroprusside; D001120:Arginine; D000109:Acetylcholine