DIET-INDUCED ATHEROSCLEROSIS INHIBITS RELEASE OF NORADRENALINE FROM SYMPATHETIC-NERVES IN RABBIT ARTERIES

Contractile responses to sympathetic nerve stimulation and exogenous n oradrenaline were compared in aortas and pulmonary arteries of control rabbits and rabbits fed a cholesterol-rich diet (0.3%) for 16 or 30 w eeks. The diet-induced atherosclerosis reduced the contractions to inc reasing concentrations of exogenous noradrenaline (0.1 nM to 10 mu M) in both arteries, and the reduction was more pronounced after 30 weeks of the hypercholesterolemia. The contractions produced with increasin g frequencies of electrical stimulation (1-32 Hz) were nearly abolishe d in the atherosclerotic arteries. Labeling of the aorta and the pulmo nary arteries with [H-3]noradrenaline resulted in accumulation of radi oactivity in both control and atherosclerotic blood vessels. After mou nting the labeled blood vessels for superfusion, a basal efflux of [H- 3]noradrenaline and of H-3-metabolites was detected. In the atheroscle rotic arteries, a decreased efflux of the intraneuronal deaminated met abolites 3,4-dihydroxyphenyl glycol (DOPEG) and 3,4-dihydroxymandelic acid (DOMA) was detected. Electrical stimulation at 1 Hz (pulmonary ar tery) or 2 Hz (aorta) caused an augmented efflux of total H-3 from the control arteries; this was mostly due to release of intact [H-3]norad renaline. The electrical impulses evoked significantly less (16 weeks) or no (30 weeks) release of [H-3]noradrenaline in the atherosclerotic arteries. These data illustrate that diet-induced atherosclerosis exe rts an inhibitory action on the sympathetic nerve terminals in the aor ta 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 a lso inhibits the intraneuronal deamination of the sympathetic transmit ter.