Investigation of endogenous nitric oxide vascular function in the carotid artery of cholesterol-fed rabbits.
1. The function of endogenous nitric oxide (NO) at the level of vascular smooth muscle, was assessed in a popular experimental model of accelerated atherosclerosis, the cholesterol-fed rabbit. 2. Endothelium-dependent vasorelaxation in response to acetylcholine (ACh, 1 microM) was significantly impaired in the carotid artery from rabbits maintained on a 1% (W/W) cholesterol diet for 8-10 weeks. Furthermore, the ability of an inhibitor of nitric oxide synthase (NOS), NG-nitro-L-arginine methyl ester (L-NAME, 1-300 microM), to enhance the contractile reactivity to a submaximal concentration of noradrenaline (NA, 3 microM), was significantly attenuated in hypercholesterolaemia. 3. A significant linear correlation between the maximal contractile effect of L-NAME (300 microM) and maximal vasorelaxation to ACh (1 microM) was determined in the carotid artery from control rabbits. In contrast, no such linear correlation was found in the carotid artery from hypercholesterolaemic rabbits. 4. We conclude that there are lesions both in agonist-stimulated, endogenous NO-dependent vasorelaxation and in the regulation of vasoconstrictor reactivity by endogenous NO in the hypercholesterolaemic rabbit carotid artery. Furthermore, the normal linear relationship between the contractile effect of L-NAME and vasorelaxation to ACh is lost after cholesterol-feeding.
Laight
D W
DW
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London.
Matz
J
J
Caesar
B
B
Carrier
M J
MJ
Anggård
E E
EE
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001161:Arteriosclerosis / Q000503:physiopathology; D002339:Carotid Arteries / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects
D002791:Cholesterol, Dietary; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D002784:Cholesterol; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester