The L-arginine-nitric oxide pathway in the canine femoral vascular bed: in vitro and in vivo experiments.
Vascular endothelial cells synthesize nitric oxide from L-arginine, and this pathway can be inhibited by various analogues of L-arginine, including NG-nitro L-arginine methyl ester (L-NAME). To investigate the role of this pathway in the regulation of femoral arterial tone, the effect of L-NAME was studied in vitro in isolated canine femoral arteries suspended in organ chambers for isometric tension recording, and in vivo in conscious dogs chronically instrumented for the measurement of iliac blood flow and iliac artery diameter. In vitro, L-NAME induced an endothelium-dependent contraction, inhibited the endothelium-dependent relaxations to acetylcholine or bradykinin, and potentiated the relaxation evoked by the nitric oxide donor SIN-1. In vivo, locally administered L-NAME induced a decrease in iliac artery diameter and an increase in iliac resistance, potentiated the iliac responses to the organic nitrate nitroglycerin, but did not affect the iliac responses to the endothelium dependent vasodilator acetylcholine. Thus, in the canine femoral vascular bed: a) basal release of nitric oxide contributes in vivo to the maintenance of a permanent vasodilator tone at the level of both large conductance and small resistance vessels; b) the endothelium-dependent relaxations to acetylcholine and bradykinin in vitro are mostly mediated through the release of nitric oxide from L-arginine; c) the endothelium-dependent relaxations to acetylcholine in vivo are probably mediated by a relaxing factor distinct from nitric oxide, or by a nitric oxide-like molecule released from endothelial pools; and d) removal of the NO-mediated vasodilator tone by L-NAME leads to a supersensitivity to nitrovasodilators, both in vitro and in vivo.
Richard
V
V
Département de Pharmacologie, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France.
Gosgnach
M
M
Drieu la Rochelle
C
C
Giudicelli
J F
JF
Berdeaux
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005263:Femoral Artery / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009569:Nitric Oxide; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine; D005996:Nitroglycerin; D000109:Acetylcholine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester