Insulin resistance and changes in chronotropic responses to adrenergic and cholinergic agonists in isolated rat atria

Objectives : To determine the effects of β -adrenoceptor and muscarinic agonists on the contractile rate of isolated right atria of rats fed a high fructose diet with or without rosiglitazone (RSG).
Materials and Methods : Male Sprague Dawley rats were assigned to four groups and given ad libitum access to one of the following diets: standard chow, standard chow supplemented with 4 mg/kg/day RSG, a high fructose diet and a high fructose diet with 4 mg/kg/day RSG. All the groups were maintained on these regimens for three weeks with weekly measurements of systolic blood pressure and body weight. At the end of the three weeks, the rats were exsanguinated and the hearts were rapidly removed following which blood glucose, insulin and lipid profiles were estimated. The right atria were isolated from the heart and their responsiveness to sympathetic and parasympathetic agonists was studied.
Results : Basal, spontaneous, isolated atrial pacemaker rate was diminished in fructose-fed rats. The maximum pacemaker rate to isoproterenol or norepinephrine was unchanged in fructose-fed rats. Further, the increase in atrial rate and half maximal effective concentration values for each agent were also unaffected. The sensitivity to negative chronotropic action of acetylcholine was enhanced in fructose fed rats, whereas the response to carbachol was unchanged. The increased sensitivity to acetylcholine was restored by RSG treatment.
Conclusion : High fructose diet induced insulin resistance and hypertension with alterations in basal spontaneous pacemaker, enhanced sensitivity to cholinergic agonist without any changes in the response to adrenergic and cholinergic receptor activation. Treatment with insulin sensitizer rosiglitazone was able to prevent all these changes. The present study suggests that rosiglitazone may have effect on the cardiovascular system in addition to the insulin sensitising action.

Keywords
Insulin resistance, β -adrenoceptor, muscranic receptor, isolated atria, insulin sensitizer