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Investigation of endogenous nitric oxide vascular function in the carotid artery of cholesterol‐fed rabbits
Author(s) -
Laight David W.,
Matz Jørgen,
Caesar Ben,
Carrier Martin J.,
Änggård Erik E.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15308.x
Subject(s) - nitric oxide , endogeny , cholesterol , medicine , cardiology , carotid arteries , artery , endothelium derived relaxing factor , chemistry
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 μ m ) 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), N G ‐nitro‐L‐arginine methyl ester (L‐NAME, 1–300 μ m ), to enhance the contractile reactivity to a submaximal concentration of noradrenaline (NA, 3 μ m ), was significantly attenuated in hypercholesterolaemia. 3 A significant linear correlation between the maximal contractile effect of L‐NAME (300 μ m ) and maximal vasorelaxation to ACh (1 μ m ) 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.