Baroreflex and chemoreflex dysfunction in streptozotocin-diabetic rats

Abstract

Several investigators have demonstrated that streptozotocin (STZ) diabetes induces changes in the autonomic control of the cardiovascular system. Changes in cardiovascular function may be related to peripheral neuropathy. The aim of the present study was to analyze changes in heart rate (HR) and arterial pressure (AP) as well as baroreflex and chemoreflex sensitivity in STZ-induced diabetic male Wistar rats (STZ, 50 mg/kg, iv, 15 days). Intra-arterial blood pressure signals were obtained for control and diabetic rats (N = 9, each group). Data were processed in a data acquisition system (CODAS, 1 kHz). Baroreflex sensitivity was evaluated by measuring heart rate changes induced by arterial pressure variation produced by phenylephrine and sodium nitroprusside injection. Increasing doses of potassium cyanide (KCN) were used to evaluate bradycardic and pressor responses evoked by chemoreflex activation. STZ induced hyperglycemia (447 ± 49 vs 126 ± 3 mg/dl), and a reduction in AP (99 ± 3 vs 118 ± 2 mmHg), resting HR (296 ± 11 vs 355 ± 16 bpm) and plasma insulin levels (16 ± 1 vs 57 ± 11 µU/ml). We also observed that the reflex bradycardia (-1.68 ± 0.1 vs -1.25 ± 0.1 bpm/mmHg, in the diabetic group) and tachycardia (-3.68 ± 0.5 vs -1.75 ± 0.3 bpm/mmHg, in the diabetic group) produced by vasopressor and depressor agents were impaired in the diabetic group. Bradycardia evoked by chemoreflex activation was attenuated in diabetic rats

Influence of fluvastatin on cardiac function and baroreflex sensitivity in diabetic rats

“…Interestingly, the increase of ΔHR/ΔMABP, an indicator of BRS, was greater in DM rats compared with Ctr rats in response to PE and SNP injections. This result is not consistent with those of some DM models, which may be largely attributed to the different time course of development for diabetes (ie, 12, 24, and 48 weeks): metabolic disorders caused by a hyperglycemic state or insulinopenia may be related to time-dependent changes in parasympathetic and sympathetic control [25,26] and different osmotic diuresis after the DM model was established [27,28] . In addition, discrepancies in species, experimental design and diabetic inducer may also affect the results to some extent [29,30] .…”

Cardiovascular control in experimental diabetes

“…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. Kuntscherova and Vlk (19) found decreased acetylcholine concentrations in isolated auricles of diabetic rats and Tomlinson et al (11) observed functional defects in cardiac cholinergic nerves in diabetic rats with vagal dysfunction.…”

“…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).…”

“…Rats treated with STZ display many of the features seen in human subjects with uncontrolled diabetes mellitus, including hyperglycemia, hypoinsulinemia, increased urinary glucose levels and consequently polyuria, as well as weight loss (9)(10)(11).…”

“…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.…”