Relationship between cardiovascular dysfunction and hyperglycemia in streptozotocin-induced diabetes in rats

Abstract

Streptozotocin (STZ)-induced diabetes in rats is characterized by cardiovascular dysfunction beginning 5 days after STZ injection, which may reflect functional or structural autonomic nervous system damage. We investigated cardiovascular and autonomic function, in rats weighing 166 ± 4 g,[5][6][7]14,30, 45, and 90 days after STZ injection (N = 24,33,27,14,and 13, respectively). Arterial pressure (AP), mean AP (MAP) variability (standard deviation of the mean of MAP, SDMMAP), heart rate (HR), HR variability (standard deviation of the normal pulse intervals, SDNN), and root mean square of successive difference of pulse intervals (RMSSD) were measured. STZ induced increased glycemia in diabetic rats vs control rats. Diabetes reduced resting HR from 363 ± 12 to 332 ± 5 bpm (P < 0.05) 5 to 7 days after STZ and reduced MAP from 121 ± 2 to 104 ± 5 mmHg (P = 0.007) 14 days after STZ. HR and MAP variability were lower in diabetic vs control rats 30-45 days after STZ injection (RMSSD decreased from 5.6 ± 0.9 to 3.4 ± 0.4 ms, P = 0.04 and SDMMAP from 6.6 ± 0.6 to 4.2 ± 0.6 mmHg, P = 0.005). Glycemia was negatively correlated with resting AP and HR (r = -0.41 and -0.40, P < 0.001) and with SDNN and SDMMAP indices (r = -0.34 and -0.49, P < 0.01). Even though STZ-diabetic rats presented bradycardia and hypotension early in the course of diabetes, their autonomic function was reduced only 30-45 days after STZ injection and these changes were negatively correlated with plasma glucose, suggesting a metabolic origin.

Chronic treatment with vascular endothelial growth factor preserves agonist-evoked vascular responses in the streptozotocin-induced diabetic rat

“…In fact, SMA conductance was much higher in STZ-diabetic rats than in SD rats. Alternatively, the lower blood pressure could be related to hypovolaemia secondary to osmotic diuresis, or to myocardial dysfunction [25,26]. Chronic treatment with VEGF was able to preserve baseline MBP in anaesthetised STZ rats, but this was not accompanied by corresponding decreases in SMA conductance.…”

Autonomic Modulation of Arterial Pressure and Heart Rate Variability in Hypertensive Diabetic Rats

“…Our laboratory observed similar results in a previous study, which demonstrated that heart rate and MAP variability were strongly correlated with urinary and plasmatic glucose. 11,23 Sympathetic hyperactivity associated with reduced cardiac vagal function and blunted baroreflex sensitivity has been shown in SHR, 27,36 while depressed baroreflex sensitivity and changes in intrinsic heart rate have been reported in STZ-diabetic rats. 5,6 In the present study, the association of hypertension and diabetes seemed not to significantly change the previously observed impairment of the cardiac function in normotensive diabetic rats.…”

“…Similarly, we have previously demonstrated decreased MAP variability in experimental normotensive diabetic rats. 11,23 It is well-known that in humans and in rat animal models, the low frequency oscillations of blood pressure correspond to the influence of the sympathetic fibers acting on the cardiovascular system. 16,33,34 This reduced sympathetic influence on blood vessels could explain, at least in part, the lower blood pressure and its variability found in this SHR+DM group.…”

“…17 Administration of STZ is a well-established method to induce diabetes in rodents, 21 producing a number of cardiovascular changes such as hypotension, bradycardia, decreased AP variability, and impairment of the reflex control of circulation. 4,19,22,23 Since the administration of STZ to Wistar rats induces a diabetic state that is not accompanied by hypertension, 11 its use in spontaneously hypertensive rats (SHR) can produce an animal model more closely related to human diabetes. Therefore, the aim of the present study was to evaluate the autonomic modulation of the cardiovascular function in STZ-induced diabetic SHR, by studying the blood pressure and heart rate variability in the time and frequency domains (spectral analysis), and also evaluating the cardiac baroreflex sensitivity in this model.…”

Efeitos fisiológicos do treinamento físico em pacientes portadores de diabetes tipo 1

“…A redução nos fluxos sangüíneos renal, cardíaco e muscular decorrentes do DM por STZ também é atenuada após o condicionamento físico (41). Não se pode descartar que o melhor controle metabólico induzido pelo treinamento físico possa ter colaborado para a melhora das variáveis cardiovasculares estudadas, tendo em vista resultados prévios de nosso grupo demonstrando que as variáveis metabólicas correlacionam-se com as alterações cardiovasculares características deste modelo (42).…”