In order to assess the effect of hypercholesterolemia on cardiac sympathetic nerve function, New Zealand white rabbits were fed a normal diet (the control group) or one enriched with 0.5% cholesterol [the hypercholesterol (HC) group] for 3 months. Before and after the 3-month diet treatment, we performed serial imaging examinations and analyzed the uptake and washout ratio of (123)I-meta-iodobenzylguanidine ((123)I-MIBG) from the myocardium by administration of (123)I-MIBG through an ear vein. At the end of the experiments, the rabbits were sacrificed, and right ventricular strips were taken from their hearts. The inotropic response of the right ventricular strips to isoproterenol (ISO) and norepinephrine (NE) were evaluated. The cardiac MIBG uptake of the HC group, which was evaluated using the heart to mediastinum ratio, was higher than that of the age-matched control group. However, the washout ratios of (123)I-MIBG did not differ statistically between the two groups. On pretreatment with cocaine, NE-enhanced contractility was greater in papillary muscles isolated from the HC group. The concentration-response curve to ISO was shifted to the right in the HC group, compared with that in the control group. In conclusion, hypercholesterolemia in rabbits resulted in an increase in sympathetic nerve density in the myocardium, a decrease in the inotropic response to ISO and an increase in the inotropic response to NE in cocaine-treated myocardium. Both the in vivo and in vitro studies demonstrated the functional significance of neural remodeling induced by hypercholesterolemia.
Copyright 2004 National Science Council, ROC and S. Karger AG, Basel