Increased sensitivity to norepinephrine cardiac arrhythmias in the deoxycorticosterone acetate high salt rat before the onset of hypertension

Abstract

To determine whether salt loading increases the sensitivity of the myocardium to fatal arrhythmias induced by norepinephrine, four groups of Sprague–Dawley rats were studied. Group I received both saline (0.9%) as drinking water and deoxycorticosterone acetate (DOCA) (0.5 mg/kg, 3 times) for 14 days (DOCA high salt group); group II received only 0.9% saline as drinking water (high salt group); group III received DOCA in the same dose regime, but tap water to drink (DOCA group); and group IV received tap water (control). Under pentobarbital anesthesia, norepinephrine was infused and electrocardiogram and blood pressure were monitored. The DOCA high salt group developed arrhythmias significantly (p < 0.05) earlier than at lower norepinephrine doses. The dose at which 50% mortality occurred was 20 μg∙kg−1∙min−1 in DOCA high salt group, 37 μg∙kg−1∙min−1 in high salt group, 40 μg∙kg−1∙min−1 in the control, and 44 μg∙kg−1∙min−1 in the DOCA group. The cumulative dose of norepinephrine associated with 50% mortality was 160 μg/kg in the DOCA high salt group, 370 μg/kg in the high salt group, 530 μg/kg in the control group, and 600 μg/kg in the DOCA group. The blood pressure after sodium loading before norepinephrine infusion was similar in all three groups. The blood pressure response to norepinephrine was not significantly different between the four groups. Myocardial content of the electrolytes Na+, K+, Mg2+, and Ca2+, were not significantly different between three of the groups, namely those receiving DOCA plus high salt, high salt or neither DOCA nor high salt as ascertained in other animals who were treated according the the three protocols. These data suggest that excess dietary sodium enhances the sensitivity to norepinephrine-induced cardiac arrhythmias.