Hemodynamic consequences of endogenous hyperinsulinism in obese rats with lesions of the ventromedial hypothalamus

The rat with ventromedian hypothalamus lesions (VMH) is characterized by massive obesity, hyperinsulinemia, increase in parasympathetic tonus and sympathetic depression. The aim of this study was to examine in this model the hemodynamic changes and the baroreflex response and to compare the data with the evaluation of beta adrenergic sensitivity. In VMH rats and Sham operated rats hemodynamic parameters were followed until 8 weeks after operation. Heart rate (HR) and blood pressure (BP) were monitored each week during 24 hours by a telemetric system, a catheter being implanted in aorta. In VMH, HR was significantly lower by the first week (p = 0.02) and until the last measurement. Systolic BP increased progressively in the two groups but was higher in VMH only at 8 weeks (p = 0.03). Compared with Sham rats, 5 days after operation, the percentage of HR acceleration in response to atropine and isoprenaline was significantly higher in VMH, whereas HR response to sodium nitroprussiate was similar in the two groups. Plasma epinephrine and norepinephrine levels were significantly higher in VMH rats. The density of cardiac beta receptors decreased from 15 days to 3 months after operation, similarly in VMH and Sham rats. The affinity of cardiac beta receptors remained stable during the same period and very similar in VMH and Sham rats. This study suggests that in VMH rats 1. bradycardia results mainly from an increase in parasympathetic tone; 2. the increase in reflex tachycardia described in normal rats after insulin infusion needs a normal activity of the sympathetic nervous system; 3. catecholamine levels may be increased despite sympathetic depression, probably as a result of an increase in adrenomedullary secretion possibly due to endogenous hyperinsulinemia; 4. the lack of hypertension in this model including a massive obesity is likely to result from the proper vasodilatory effect of insulin.