Sympathetic tone assessed by washout of iodine 125-labeled metaiodobenzylguanidine from the murine left ventricle--influence of immobilization stress and inhibition of the renin-angiotensin system

Abstract

Background: Because it is not metabolized as is norepinephrine (NE), most of the metaiodobenzylguanidine (MIBG) taken up by the heart is considered to be lost subsequently by release concomitant with sympathetic stimulation. Therefore we examined whether the washout of MIBG is influenced by sympathetic tone, which we modulated by using immobilization stress or activation of the renin-angiotensin system (RAS).

Methods and results: In 175 male ddY mice, left ventricular radioactivity was counted 30 minutes or 4 hours after injection of 74 kBq (2 microCi) of iodine 125- or iodine 131-labeled MIBG (125I- or 131I-MIBG). The washout rates of MIBG were determined under immobilization stress or under sodium loading or restriction in combination with losartan (10 mg/kg) or cilazapril (1 mg/kg) pretreatment. Immobilization enhanced the washout of 125I-MIBG (80.9% vs 57.9% in the control animals); this was determined to be related to washout from the neuronal compartment, because the nonneuronal component assessed through desipramine pretreatment was not affected. Pretreatment with losartan or cilazapril decreased the facilitation of 125I-MIBG washout in sodium-restricted mice (40.9% and 33.7%, respectively, vs 43.5% in the control animals), but not in sodium-loaded mice.

Conclusions: Measurement of MIBG washout may be feasible for determining the changes in sympathetic tone caused by immobilization stress or activation of the RAS.