Vascular activity of polycations and basic amino acids: L-arginine does not specifically elicit endothelium-dependent relaxation.
Irrespective of their stereochemistry (D- or L-form), polycations such as poly-lysine, poly-arginine and poly-histidine elicited endothelium dependent relaxation of pre-contracted rat aortic rings in a dose-dependent manner (ED50 less than or equal to 10-7 M). In contrast, the basic amino acids arginine, glutamine, histidine and lysine caused only endothelium-potentiated relaxation at high concentrations (ED 50 greater than 10-3 M). Both heparin (1U/ml) and dextran sulphate (10 microgram/ml) abolished relaxation by the polycations but had no effect on the responses to the basic amino acids or acetylcholine. These results indicate that the vasodilatory property of the polycations is due to an electrostatic interaction with anionic domains on the endothelial surface, whereas the basic amino acids elicit a non-specific relaxation. Therefore, L-arginine per se cannot be the immediate precursor of nitric oxide, the proposed endothelium-derived relaxing factor.
Thomas
G
G
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, D.C. 20007
Hecker
M
M
Ramwell
P W
PW
D000109:Acetylcholine / Q000494:pharmacology; D000599:Amino Acids, Diamino / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology*; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects
D000599:Amino Acids, Diamino; D003911:Dextrans; D006493:Heparin; D016264:Dextran Sulfate; D001120:Arginine; C009727:benzoylarginine ethyl ester; D000109:Acetylcholine