Evaluation of Hemodynamics, Vascular Reactivity and Baroreceptor Compensation in the Insulin Resistant Zucker Obese Rats

Pamidimukkala, Jaya; Jandhyala, Bhagavan S.

doi:10.3109/10641969609081036

Cited by 37 publications

(43 citation statements)

References 22 publications

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“…Plasma glucose level and blood pressure in Zucker-fatty rats are relatively similar to those in Zucker-lean rats [14,20]. These characteristics show that the Zucker-fatty rat may be suitable for research on effects of insulin resistance on autonomic nervous function.…”

Section: Introductionmentioning

confidence: 52%

Characteristics of Autonomic Nervous Function in Zucker-Fatty Rats: Investigation by Power Spectral Analysis of Heart Rate Variability.

2004

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Abstract:We investigated the characteristics of autonomic nervous function in Zucker-fatty and Zucker-lean rats. For this purpose, a long-term electrocardiogram (ECG) was recorded from conscious and unrestrained rats using a telemetry system, and the autonomic nervous function was investigated by power spectral analysis of heart rate variability (HRV). Although heart rate (HR) in Zucker-fatty rats was lower than that in Zucker-lean rats throughout 24 h, apparent diurnal variation in HR was observed in both strains and HR during the dark period was significantly higher than that in light period. Diurnal variation in locomotor activity (LA) in Zucker-fatty rats was also observed, but LA was lower than that in Zucker lean rats, especially during the dark period. There were no significant differences, however, in high-frequency (HF) power, low-frequency (LF) power, and the LF/HF ratio between Zucker-fatty and Zucker-lean rats. The circadian rhythm of these parameters was mostly preserved in both strains of rats. Moreover, the effect of autonomic blockades on HRV was nearly the same in Zucker-fatty and Zucker-lean rats. These results suggest that the autonomic nervous function of insulin-resistant Zucker-fatty rats remain normal, from the aspect of power spectral analysis of HRV.

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Section: Introductionmentioning

confidence: 52%

Characteristics of Autonomic Nervous Function in Zucker-Fatty Rats: Investigation by Power Spectral Analysis of Heart Rate Variability.

2004

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“…Zucker rats have been described as being both hypertensive and normotensive. Several studies indicate that ZFR are hypertensive compared with phenotypically normal heterozygous insulin-sensitive ZLR (1,10,24,50), whereas other studies show a normotensive state of ZFR (30,35,36). Several studies (10,19,45,47) indicate higher levels of SNA in homozygous Zucker rats than in phenotypically normal heterozygous Zucker rats (fa/Ϫ), and it has been suggested that alterations in sympathetic function in obese Zucker rats can be tissue specific (30).…”

Section: Discussionmentioning

confidence: 99%

“…Homozygous Zucker rats are insulin resistant, hyperinsulinemic, and obese. Previous studies on the link between alterations of blood pressure and SNA in the presence of insulin resistance in this strain have yielded contradictory results (1,10,19,24,30,35,36,47,50) that might to be caused, in part, by limitations of the assessment of the degree of alterations of glucose kinetics.We showed previously in the spontaneously hypertensive rat (SHR) and its related control strain (33, 34) that a suitable characterization of the dynamics of glucose kinetics is obtained from the intravenous glucose tolerance test (IVGTT) interpreted with the minimal model (4, 16). On the other hand, an important index of SNA is provided by somatosympathetic reflexes, which are coordinated autonomic responses to activation of somatic afferents mediated by changes in sympathetic activity that cause a cardiovascular reaction to changes in the physical state of the body (14,40).…”

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confidence: 90%

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Enhanced sympathetic reactivity associates with insulin resistance in the young Zucker rat

Ruggeri¹,

Brunori²,

Cogo³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Somatosympathetic reflexes were studied in young hyperinsulinemic, insulin-resistant (Zucker fatty) rats (ZFR) and a related control (Zucker lean) strain (ZLR). Glucose metabolism was characterized by minimal model analysis of intravenous glucose tolerance test data. Seven-week-old ZFR (n ϭ 18) and ZLR (n ϭ 17) were studied under pentobarbital anesthesia. Mean body weight and plasma glucose and insulin concentration were significantly greater (P Ͻ 0.05) in ZFR than in ZLR, whereas basal values of mean arterial pressure (MAP) and heart rate (HR) were not significantly different. Increments of MAP (⌬MAP) and HR (⌬HR) elicited by electrical stimulation of the sciatic nerve (5-s trains of 100 pulses, 0.5-ms pulse duration, 100-to 400-A pulse intensity) were significantly higher (ANOVA, P Ͻ 0.05) in ZFR at each level of stimulus intensity. Regression analysis showed a linear increase in ⌬MAP and ⌬HR with increasing sciatic nerve stimulus intensity. Pressor responses to phenylephrine after ganglionic blockade demonstrated that vascular reactivity to adrenergic stimulation is not increased in ZFR compared with ZLR. Thus this factor does not contribute to enhancement of somatosympathetic reflexes observed in this strain. Insulin sensitivity in ZFR was onefourth (P Ͻ 0.05) that in ZLR. These results suggest that stronger sympathetic nervous reactivity in ZFR is associated with a severe insulin-resistant state before the onset of hypertension and support the hypothesis that insulin-mediated stimulation of the sympathetic nervous system is involved in the development of cardiovascular diseases related to alterations of glucose metabolism. sympathetic nervous activity; minimal model analysis; glucose kinetics; hypertension HYPERINSULINEMIA AND INSULIN resistance are considered important risk factors for development of hypertension (2, 39), and a number of studies have shown a significant association between hypertension and insulin resistance in obese and nonobese individuals (12,15,27,28,46). However, the pathophysiological relation among hyperinsulinemia, insulin resistance, and hypertension remains poorly understood.Some experimental reports suggest that an increase in sympathetic nervous system activity (SNA) may play a role in the association between insulin resistance and elevated blood pressure (39). This association might be due to a primary increase in sympathetic activity (22). Although an increase in sympathetic activity can cause hypertension and insulin resistance, studies performed on animal models indicate that the insulin resistance induced by a high-lipid diet occurs before the onset of hypertension (20), suggesting the primacy of the insulinmediated stimulation of the sympathetic nervous system. If this is true, a suitable animal model to investigate the mechanisms underlying insulin resistance and its associated pathologies is the obese Zucker rat, homozygous for the fa allele (fa/fa), in which a mutation of the leptin receptor-coding gene impairs the ability of leptin to suppress food intake. Homozygous ...

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“…[17][18] Enhanced central sympathetic discharge, abnormal hemodynamics and attenuated BRS were found in obese Zucker rats. [19][20] Even normotensive, obese Zucker rats have impaired chronotropic baroreflexes. 20 The blunted baroreflex may contribute to initial blood pressure elevation and further cause hypertension in obesity.…”

Section: Introductionmentioning

confidence: 99%

Altered nitroxidergic and NMDA receptor-mediated modulation of baroreflex-mediated heart rate in obese Zucker rats

et al. 2010

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Arterial baroreflex, an important physiological regulatory system for buffering systemic blood pressure, is impaired in obesity. This study investigated whether the blunted baroreflex function in obesity is attributed to the altered nitroxidergic or N-methyl-Daspartate (NMDA) mechanism. Baroreflex bradycardia responses, blood pressure and heart rate in 30 lean and 30 obese anesthetized Zucker rats (8-12 weeks of age) were assessed after injecting phenylephrine with intravenous preadministration of saline (control), dextromethorphan (DXM, NMDA receptor antagonist, 10 mg kg À1 ) or N(G)-nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor, 100 mg kg À1 ). Compared with lean rats (À2.00 ± 0.29 b.p.m. mm Hg À1 ), the baroreflex sensitivity (BRS) in obese rats (-0.43±0.05 b.p.m. mm Hg À1 ) was significantly blunted. The BRS was significantly suppressed by DXM in lean rats but not in obese rats. After administration of L-NAME, BRS was significantly suppressed in lean Zucker rats but not in obese Zucker rats. The normal BRS was significantly suppressed in lean rats after administration of both DXM and L-NAME, and the blunted BRS in obesity was significantly blocked to nearly no BRS after administration of both DXM and L-NAME. This study suggests that BRS is blunted in obese rats and that blunted baroreflex is, at least in part, attributed to altered nitroxidergic or NMDA receptor-mediated modulation.

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Evaluation of Hemodynamics, Vascular Reactivity and Baroreceptor Compensation in the Insulin Resistant Zucker Obese Rats

Cited by 37 publications

References 22 publications

Characteristics of Autonomic Nervous Function in Zucker-Fatty Rats: Investigation by Power Spectral Analysis of Heart Rate Variability.

Characteristics of Autonomic Nervous Function in Zucker-Fatty Rats: Investigation by Power Spectral Analysis of Heart Rate Variability.

Enhanced sympathetic reactivity associates with insulin resistance in the young Zucker rat

Altered nitroxidergic and NMDA receptor-mediated modulation of baroreflex-mediated heart rate in obese Zucker rats

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