Depletion of arterial L-arginine causes reversible tolerance to endothelium-dependent relaxation.
This study examined the influence of lowered arterial levels of L-arginine on endothelium-dependent relaxation of isolated rings of bovine pulmonary artery. Incubation of arterial rings under tension for 24 hr in oxygenated Krebs bicarbonate solution at 37 degrees C resulted in the development of marked or complete tolerance to A23187 (calcium ionophore)- and acetylcholine-elicited relaxation. Relaxant responses to nitric oxide were unaffected. Addition of L-arginine did not relax control rings but did elicit marked endothelium-dependent relaxation of tolerant rings that was inhibited by oxyhemoglobin or methylene blue. L-Arginine also restored acetylcholine-elicited relaxation. Inclusion of L-canavanine in the 24 hr incubations protected against the development of tolerance. The tissue concentration of arginine was 3-fold lower in tolerant than control arterial rings and L-canavanine restored arterial arginine levels to control values. Therefore, depletion of arterial L-arginine causes reversible tolerance to endothelium-dependent relaxation.
Gold
M E
ME
Department of Pharmacology, UCLA School of Medicine Center for Health Sciences 90024.
Bush
P A
PA
Ignarro
L J
LJ
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000032:analysis / Q000097:blood* / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D007536:Isomerism; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology
D010108:Oxyhemoglobins; D009569:Nitric Oxide; D000001:Calcimycin; D001120:Arginine; D000109:Acetylcholine