Blockade of endothelium-derived relaxing factor synthesis with NG-nitro-L-arginine methyl ester leads to enhanced venous reactivity in vivo.
This study was performed to examine whether endothelium-derived relaxing factor (EDRF) influences venous tone and reactivity in vivo. The inferior vena cava and abdominal aorta were studied simultaneously under continuous haemodynamic monitoring in anaesthetised rabbits. In addition, a 20-MHz intravascular ultrasound catheter was placed in the vena cava for on-line two-dimensional imaging of vessel cross-sectional area and calculation of wall stress (T(ension) = P(mean) * r(adius)/2). This approach enabled simultaneous visualisation of both venous (CA(ven)) and aortic (CA(art)) cross-sectional area with continuous recording of vessel dimensions. Measurements were made before and after administration of NG-nitro-l-arginine methyl ester (L-NAME; 10 mg.kg i.v.), a specific inhibitor of EDRF biosynthesis. After L-NAME there was a significant increase in central venous pressure and a decrease in CA(ven). On the arterial side, L-NAME caused a significant increase in mean pressure and CA(art), resulting in a significantly augmented arterial wall stress. The venodilatation elicited by increasing doses of glyceryltrinitrate was markedly enhanced after L-NAME. Norepinephrine caused a parallel shift of the dose-response curve for CA(ven) in the presence of a lower baseline value. These results suggest that EDRF contributes substantially to the control of large capacitance veins in vivo and that L-NAME increases venous reactivity to both norepinephrine and glyceryltrinitrate.
Schwarzacher
S
S
Department of Cardiovascular Pharmacology, University of Vienna, Austria.
Weidinger
F
F
Schemper
M
M
Raberger
G
G
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002496:Central Venous Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*; D014682:Vena Cava, Inferior / Q000187:drug effects*
D009569:Nitric Oxide; D001120:Arginine; D005996:Nitroglycerin; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine