Modulation of left ventricular iodine-125-MIBG accumulation in cardiomyopathic Syrian hamsters using the renin-angiotensin system.

UNLABELLED

Genetically inbred cardiomyopathic hamsters were examined to investigate the mechanism of reduced myocardial accumulation of metaiodobenzylguanidine (MIBG) in the cardiomyopathic heart.

METHODS

Bio 14.6 Syrian hamsters (hypertrophic stage: n = 15, early heart failure stage: n = 17) and control F1b strain golden hamsters (n = 36) were injected with 296 kBq of [125I] MIBG and killed 30 min or 4 hr later. Thirty-three of these hamsters were pretreated with 10 mg/kg of desipramine to determine non-neuronal MIBG accumulation. To evaluate the nonexocytotic MIBG release from nerve endings, desipramine was administered to four Bio 14.6 hamsters 15 min after [125I]MIBG injection. To determine the role of the activated renin-angiotensin system (RAS) in MIBG washout from sympathetic nerve terminals in cardiomyopathy at early heart failure stage, 10 mg/kg/day cilazapril, an angiotensin-converting enzyme inhibitor, was given orally to 7 controls and 16 cardiomyopathic hamsters for 16 wk.

RESULTS

In the absence of desipramine pretreatment, left ventricular [125I]MIBG accumulation 4 hr after injection was 0.376% +/- 0.015 %kg dose/g (mean +/- s.e.m.) in the hypertrophic hamsters (versus 0.418 +/- 0.019 in controls of the same age; ns), and 0.195 +/- 0.025 in early heart failure hamsters. Treatment with cilazapril partially restored MIBG accumulation in the Bio 14.6 hamsters but did not affect the controls.

CONCLUSION

Decreased [125I]MIBG accumulation in cardiomyopathic hamsters during the early heart failure stage is caused by neuronal release which is partially modulated by the activated RAS.