Autonomic Dysfunction in Short-term Experimental Diabetes

Abstract

Previous data showed that diabetes induced by streptozotocin for 5 days causes changes in arterial pressure control and baroreflex regulation of heart rate in male Wistar rats. The impairment of baroreflex may be related to autonomic neuropathy as described by several investigators. The aim of this study was to identify autonomic changes in short-term experimental diabetes in rats (induced for 5 days with streptozotocin 65 mg IP). Intra-arterial blood pressure signals were obtained from 6 control group and 7 diabetic group rats and processed in a data acquisition system (CODAS, 1 kHz). Both vagal and sympathetic function were assessed through intravenous injections of methylatropine and propranolol. Streptozotocin induced hyperglycemia (18.9 +/- 1.8 versus 5.8 +/- 0.2 mmol/L) and reductions in mean arterial pressure (102 +/- 2 versus 117 +/- 3 mm Hg) and resting heart rate (298 +/- 14 versus 332 +/- 2 beats per minute). Sodium and potassium levels were not different between groups. The intrinsic heart rate was reduced in the diabetic group (302 +/- 10 versus 398 +/- 6 beats per minute). This group also exhibited depressed vagal and sympathetic tone (50% and 22%, respectively), reduction of vagal effect (42%), and no change in sympathetic effect. In conclusion, early autonomic dysfunction in short-term streptozotocin-induced diabetes seems to be related to changes in arterial pressure and baroreflex control.

Cardiovascular control in experimental diabetes

“…Studies from our laboratory have shown reduction in vagal tonus and maintenance of sympathetic tonus to the heart evaluated by pharmacological blockade with propranolol and methylatropine, respectively (14,16) (Figure 1), as previously demonstrated by Wegner et al (17), suggesting the presence of cardiac vagal neuropathy. Resting bradycardia in STZ-diabetic rats has been attributed to changes in the sinoatrial node with a consequent reduction in intrinsic HR (14,16,18), although functional alterations in the cholinergic mechanism cannot be excluded as a causal factor.…”

“…These data indicate that vagal function and intrinsic HR are decreased in short-and long-term STZ-induced diabetes in rats. The bradycardic response to methacholine injection was similar in control and diabetic rats 5 days after STZ administration (14). However, in 15-day STZ-treated rats this response was higher than in normal rats (10), suggesting that the early impairment in vagal tonus may be leading to an adaptive change in muscarinic receptors.…”

“…Resting bradycardia in STZ-diabetic rats has been attributed to changes in the sinoatrial node with a consequent reduction in intrinsic HR (14,16,18), although functional alterations in the cholinergic mechanism cannot be excluded as a causal factor. These data indicate that vagal function and intrinsic HR are decreased in short-and long-term STZ-induced diabetes in rats.…”

“…Hence, the disorders in autonomic efferent and afferent neuronal systems could have important consequences for the control of cardiovascular function. Several studies using experimental models have been conducted to investigate the mechanisms of reflex dysfunction of diabetes (10,(14)(15)(16)33,34).…”

“…The mechanisms involved in these alterations are not completely understood. Some investigators have associated bradycardia and hypotension with reduction in intrinsic HR, in vagal tonus and in cardiovascular reflex control (10,(14)(15)(16), suggesting early autonomic dysfunction. Furthermore, impairment of heart contractility and vascular responsiveness, as well as changes in blood volume caused by osmotic diuresis could be involved in the pathogenesis of these alterations.…”