High-Cholesterol Diet Induces Altered Responsiveness of Rabbit Arterial Smooth Muscle to Noradrenaline

Abstract

The potential effect of feeding a high-cholesterol atherogenic diet (HCD) on in vitro responsiveness of rabbit arterial smooth muscle was investigated. The vasoconstrictor response produced by either exogenous or endogenous (field stimulation) noradrenaline was significantly depressed in isolated segments of ear artery after HCD as compared to regular diet fed animals. On the other hand no changes to high K⁺ could be observed in arterial segments after HCD as compared to regular diet fed rabbits. In addition, the α-adrenoceptor-mediated inotropic response and contraction of bladder smooth muscle showed only minor or no changes after HCD as compared to regular diet fed rabbits.

The transcriptome profiling of diseased mouse aortas discloses a dysregulation of the sympathetic neurotransmission in atherosclerosis

“…Recent evidence seems to suggest that in the adventitia of diseased arteries, an increased amount of immune cells associates with a more abundant sympathetic innervation [ 9 ]. This finding is in contrast to what has been observed in previous studies, conducted in a variety of experimental settings and different animal models, in which a reduction in sympathetic markers/functionality was observed following the administration of diets that could promote atherosclerosis development [ [10] , [11] , [12] , [13] ].…”

“…Actually, the interplay between hyperlipidemia, atherosclerosis and sympathetic neurotransmission has been the object of several previous investigations that have evaluated the impact of elevated plasma lipids on the response of the arterial wall to catecholamines. Studies in rabbits have demonstrated that both dietary- and genetically-induced hypercholesterolemia impairs the arterial contractility as a consequence of a reduced release of endogenous noradrenaline [ 10 , 11 ]. In addition, a cholesterol-supplemented diet to rats increased by three-fold plasma cholesterol levels and attenuated the sympathetic noradrenergic neurotransmission in the tail artery, reducing its noradrenaline content [ 12 ].…”

Functional and Histological Changes in Mesenteric Arteries and Aortas from Monkeys Fed a High Cholesterol Diet

“…On the other hand, contractions induced by nor epinephrine and electrical stimulation of ad renergic nerves did not differ in the arteries from control and atherosclerotic monkeys, indicating that functions of a-adrenoceptors and adrenergic nerves may not significantly be altered by treatment with an atherogenic diet. In isolated segments of the ear artery from rabbits fed a high cholesterol diet, re sponses to endogenous and exogenous nor epinephrine are significantly depressed (14).…”