meta-iodobenzylguanidine uptake in the hypertensive-diabetic rat heart: a marker for myocardial dysfunction?
The purpose of this study was to investigate the cardiac adrenergic neuronal changes induced by diabetes and hypertension by using an analogue of norepinephrine, meta-iodobenzylguanidine (MIBG), and to compare these changes with the contractile state of ventricular papillary muscle. The tissue concentration of norepinephrine in the cardiac apex was also measured for direct comparison with [123I]MIBG uptake. One week following the induction of diabetes by streptozotocin injection (55 mg/kg, i.v.), male Sprague-Dawley rats were given subcutaneous injections of a hypertension-inducing agent, deoxycorticosterone acetate (DOCA, 25 mg/kg), or DOCA vehicle twice weekly for 3, 6, 9, or 12 weeks. At the end of each time point, the animals were injected intravenously (15 mCi/mg; 1 Ci = 37 GBq) with [123I]MIBG. The results showed a progressive decrease in MIBG uptake into the hearts of diabetic, hypertensive, and diabetic-hypertensive rats during the 12-week observation period, compared with the control group. However, length-tension papillary muscle studies at 12 weeks indicated that only the diabetic group had a diminished performance compared with control. Furthermore, an inverse relationship was observed between MIBG uptake and norepinephrine levels in the cardiac apex of the diabetic and diabetic-hypertensive groups. Therefore, we concluded that either MIBG does not provide an accurate indication of adrenergic integrity or that there is no relationship between sympathetic activity and myocardial function at the time points measured. MIBG did not prove to be a useful marker for myocardial dysfunction in diabetic rats.
Herman
L M
LM
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver.
Dai
S
S
Hartman
N G
NG
McNeill
J H
JH
D019797:3-Iodobenzylguanidine; D000320:Adrenergic Fibers; D000818:Animals; D015415:Biomarkers; D003900:Desoxycorticosterone; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D006321:Heart / Q000503:physiopathology; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D066298:In Vitro Techniques; D007462:Iodobenzenes / Q000493:pharmacokinetics*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000503:physiopathology; D013311:Streptozocin
D015415:Biomarkers; D007462:Iodobenzenes; D019797:3-Iodobenzylguanidine; D003900:Desoxycorticosterone; D013311:Streptozocin; D009638:Norepinephrine