Diet-induced atherosclerosis inhibits release of noradrenaline from sympathetic nerves in rabbit arteries.
Contractile responses to sympathetic nerve stimulation and exogenous noradrenaline were compared in aortas and pulmonary arteries of control rabbits and rabbits fed a cholesterol-rich diet (0.3%) for 16 or 30 weeks. The diet-induced atherosclerosis reduced the contractions to increasing concentrations of exogenous noradrenaline (0.1 nM to 10 microM) in both arteries, and the reduction was more pronounced after 30 weeks of the hypercholesterolemia. The contractions produced with increasing frequencies of electrical stimulation (1-32 Hz) were nearly abolished in the atherosclerotic arteries. Labeling of the aorta and the pulmonary arteries with [3H]noradrenaline resulted in accumulation of radioactivity in both control and atherosclerotic blood vessels. After mounting the labeled blood vessels for superfusion, a basal efflux of [3H]noradrenaline and of 3H-metabolites was detected. In the atherosclerotic arteries, a decreased efflux of the intraneuronal deaminated metabolites 3,4-dihydroxyphenyl glycol (DOPEG) and 3,4-dihydroxymandelic acid (DOMA) was detected. Electrical stimulation at 1 Hz (pulmonary artery) or 2 Hz (aorta) caused an augmented efflux of total 3H from the control arteries; this was mostly due to release of intact [3H]noradrenaline. The electrical impulses evoked significantly less (16 weeks) or no (30 weeks) release of [3H]noradrenaline in the atherosclerotic arteries. These data illustrate that diet-induced atherosclerosis exerts an inhibitory action on the sympathetic nerve terminals in the aorta and the pulmonary artery of the rabbit. This effect, together with an inhibitory effect at the postjunctional level results in a loss of the responsiveness to nerve stimulation. The atherosclerotic process also inhibits the intraneuronal deamination of the sympathetic transmitter.
Verbeuren
T J
TJ
Division of Angiology, Servier Research Institute, Suresnes, France.
Simonet
S
S
Herman
A G
AG
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D001161:Arteriosclerosis / Q000378:metabolism / Q000503:physiopathology*; D002791:Cholesterol, Dietary; D004558:Electric Stimulation; D006937:Hypercholesterolemia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D010477:Perfusion; D011651:Pulmonary Artery / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000378:metabolism*
D002791:Cholesterol, Dietary; D009638:Norepinephrine