Cardiac iodine-123 metaiodobenzylguanidine uptake in animals with diabetes mellitus and/or hypertension

Abstract

The aim of the present study was to evaluate the use of the noradrenaline analogue iodine-123 metaiodobenzylguanidine ([123I]MIBG) for the assessment of cardiac sympathetic activity in the presence of diabetes mellitus and/or hypertension in animal models. One model used Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) rendered diabetic at 12 weeks of age by an intravenous injection of streptozotocin (STZ). The other model used lean and obese Zucker rats. In all groups basic haemodynamic values were established and animals received an intravenous injection of 50 microCi [123I]MIBG. Initial myocardial uptake and wash-out rates of [123I]MIBG were measured scintigraphically during 4 h. After sacrifice, plasma noradrenaline and left cardiac ventricular beta-adrenoceptor density was determined. The diabetic state, both in STZ-treated rats (direct induction) and in obese Zucker rats (genetic induction), appeared to induce a lower cardiac density of beta-adrenoceptors, indicative of increased sympathetic activity. Cardiac [123I]MIBG then showed increased wash-outs, thereby confirming enhanced noradrenergic activity. This parallism of results led to the conclusion that [123I]MIBG wash-out measurements could provide an excellent tool to assess cardiac sympathetic activity non-invasively. However, in hypertension (WKY vs SHR), both parameters failed to show parallelism: no changes in beta-adrenoceptor density were found, whereas [123I]MIBG wash-out rate was increased. Thus, either [123I]MIBG washout or beta-adrenoceptor density may not be a reliable parameter under all circumstances to detect changes in the release of noradrenaline. Changes in the initial uptake of [123I]MIBG were observed as well. This may be a good marker for the disappearance of cardiac innervation, but it seems not to be a good parameter for distinguishing between loss of sympathetic innervation and enhanced uptake of noradrenaline in pathological conditions.

Evaluation of the cardiac autonomic nervous system in spontaneously non-insulin-dependent diabetic rats by123I-metaiodobenzylguanidine imaging

“…The fasting plasma glucose level in OLETF rats receiving sucrose loading was about 550 mg/dl, which is similar to that in rats with STZ-induced diabetes. 22 These results indicate that myocardial 123I-MIBG scintigraphy may be a very useful noninvasive tool for detecting an early change in diabetic cardiac function. This view is also supported by finding that CVR-R was not decreased in OLETF rats without sucrose feeding, whereas abnormalities in 123I-MIBG scintigraphy were observed.…”

“…These results are consistent with a previous study by Dubois et al of streptozotocin (STZ)-induced diabetic Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). 22 They reported that the washout rate of diabetic WKYs was higher than that of control WKYs, but there was no significant difference between STZ-SHRs and SHRs. It is well known that STZ selectively destroys pancreatic ß cells and results in a deficiency in insulin secretion.…”

Role of Long-Term Potentiation of Sympathetic Ganglia (gLTP) in Hypertension

“…Obese, insulin-resistant patients maintain higher levels of insulin and leptin, which lead to increased sympathetic activity (91). Such an increase in central sympathetic activity has been also demonstrated in OZR (86)(87)(88)(92)(93)(94)(95)(96)138), which is believed to be due to hyperinsulinemia and hypercortism (97)(98)(99)(100)139). As in obese humans, OZRs inadequately handle stress (101,102).…”

Expression of gLTP in Sympathetic Ganglia of Obese Zucker Rats In Vivo: Molecular Evidence

“…All of that lead to hypertension at later stages of life (see Kasiske et al 1992 for review). Activity of the sympathetic nervous system has been shown to be increased in OZRs (Arase et al 1989;Morgan et al 1995;Alonso-Galicia et al 1996;Dubois et al 1996;Pacak et al 1996;Pamidimukkala and Jandhyala 1996;Tonello et al 1999;Carlson et al 2000;Fang et al 2000), which could be due to hyperinsulinemia and elevated glucocorticoid levels (Landsberg and Young 1985;Cunningham et al 1986;Reaven et al 1996;Clapham and Turner 1997;Edwards et al 2000). Similar to obese humans, OZRs inadequately handle stress (Walker and Edwards 1994;Suter et al 1997).…”