The effect of hypercholesterolaemia and atherosclerosis on alpha-adrenoceptor-mediated vasoconstriction in conscious rabbits and rabbit aorta.
Rabbits were fed a diet containing 1% cholesterol for 4 or 8 weeks and the constrictor responses to alpha-adrenoceptor agonists, as well as endothelium-dependent and endothelium-independent dilatation, were examined both in vivo and in vitro. The high cholesterol diet caused a significant elevation of plasma cholesterol concentration but no macroscopic evidence of atherosclerosis after 4 weeks whereas after 8 weeks there was a significant development of atherosclerotic lesions in the thoracic and abdominal aorta. In conscious rabbits pressor responses to the non-selective alpha-adrenoceptor agonist noradrenaline and the selective alpha 1-adrenoceptor agonist phenylephrine were enhanced after 4 weeks but returned to control levels after 8 weeks on the diet. The pressor responses to the alpha 2-adrenoceptor agonist B-HT 920 were reduced by the development of atherosclerosis. In the isolated thoracic aorta from these rabbits contractile responses to noradrenaline were impaired by hypercholesterolaemia whereas responses to phenylephrine were unaffected. Endothelium-dependent relaxation was impaired by hypercholesterolaemia both in vivo and in vitro after 4 and 8 weeks on the diet whereas endothelium-independent relaxation was not affected. These results indicate that the effect of hypercholesterolaemia on alpha-adrenoceptor-mediated constriction is dependent on: (1) the absence or presence of atherosclerotic lesions, (2) the size of the artery and (3) the subtype of alpha-adrenoceptor involved in the response. There does not appear to be any relationship between the loss of endothelium-dependent relaxation in hypercholesterolaemia and the observed changes in adrenergic vasoconstriction.
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
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D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D001161:Arteriosclerosis / Q000503:physiopathology*; D001381:Azepines / Q000494:pharmacology; D001835:Body Weight; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D006937:Hypercholesterolemia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; C024763:talipexole; D005996:Nitroglycerin; D009638:Norepinephrine