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


CONCLUSIONS
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.
Takatsu
H
H
Second Department of Internal Medicine, Gifu University School of Medicine, Japan.
Uno
Y
Y
Fujiwara
H
H
D019797:3-Iodobenzylguanidine; D000818:Animals; D009202:Cardiomyopathies / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D017315:Cilazapril / Q000494:pharmacology; D003326:Coronary Circulation; D006224:Cricetinae; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000294:innervation / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D007462:Iodobenzenes / Q000493:pharmacokinetics*; D008647:Mesocricetus; D009474:Neurons / Q000378:metabolism; D011877:Radionuclide Imaging; D012084:Renin-Angiotensin System / Q000502:physiology*
D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D017315:Cilazapril; D019797:3-Iodobenzylguanidine; D003891:Desipramine