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It has been suggested that nitric oxide (NO) from iNOS source is involved in inflammation and oxidative stress, and hypertension in obese subjects involves an inflammatory process. However, no study evaluated the participation of iNOS inhibition on cardiovascular, autonomic, and inflammatory parameters in obese rats. Obesity was induced by the administration of 4 mg/g body weight of monosodium glutamate (MSG) or equimolar saline (CTR) in newborn rats. On the 60th day, treatment with aminoguanidine (Amino, 50 mg/kg), an iNOS inhibitor, or 0.9% saline, was started. On the 90th day, mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious rats and autonomic modulation was conducted with the CardioSeries software. Plasma samples were collected to assess lipid peroxidation and prostaglandins (PGE 2 ). In addition, iNOS immunohistochemistry in cardiac tissue was evaluated. MSG rats showed hypertension compared to CTR, and Amino treatment did not reverse it. Obese rats presented increased sympathetic and decreased parasympathetic modulation to the heart, reverted by Amino treatment. Plasma PGE 2 was increased in obese rats, and Amino treatment decreased. Obese rats presented increased plasma lipoperoxidation, which was decreased after Amino treatment. Also, cardiac iNOS immunohistochemistry was decreased after Amino treatment. Our data suggest that iNOS activation is involved in the systemic and cardiac mechanisms of oxidative stress, inflammation, and autonomic dysfunction derived from obesity.

Objective: Obesity-induced abnormalities, such as insulin resistance, dyslipidemia and hypertension, are frequently correlated with low-grade inflammation, a process that may depend on normal spleen function. This study investigated the role of the spleen in the obesity induced by monosodium glutamate (MSG) treatment., Materials/methods: MSG-obese and lean control (CON) rats were subjected to splenectomy (SPL) or non-operated (NO)., Results: MSG-NO rats presented a high adipose tissue content, insulin resistance, dyslipidemia and islet hypersecretion, accompanied by hypertrophy of both pancreatic islets and adipocytes when compared with CON-NO rats. In addition, changes in nitric oxide response were found in islets from the MSG-NO group without associated alterations in inducible nitric oxide synthase (iNOS) or IL1β expression. MSG-NO also presented increased leukocyte counts and augmented LPS-induced nitric oxide production in macrophages. Splenectomy of MSG-obese animals decreased insulin hypersecretion, normalized the nitric oxide response in the pancreatic islets, improved insulin sensitivity and reduced hypertrophy of both adipocytes and islets, when compared with MSG-NO rats., Conclusion: Results show that splenectomy attenuates the progression of the obesity modulating pancreas functions in MSG-obese rats., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We investigated the involvement of nitric oxide (NO) and reactive oxygen species (ROS) on autonomic cardiovascular parameters, vascular reactivity, and endothelial cells isolated from aorta of monosodium glutamate (MSG) obese rats. Obesity was induced by administration of 4 mg/g body wt of MSG or equimolar saline [control (CTR)] to newborn rats. At the 60th day, the treatment was started with N(G)-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg) or 0.9% saline. At the 90th day, after artery catheterization, mean arterial pressure (MAP) and heart rate were recorded. Plasma was collected to assess lipid peroxidation. Endothelial cells isolated from aorta were evaluated by flow cytometry and fluorescence intensity (FI) emitted by NO-sensitive dye [4,5-diaminofluoresceindiacetate (DAF-2DA)] and by ROS-sensitive dye [dihydroethidium (DHE)]. Vascular reactivity was made by concentration-response curves of acetylcholine. MSG showed hypertension compared with CTR. Treatment with L-NAME increased MAP only in CTR. The MSG induced an increase in the low-frequency (LF) band and a decrease in the high-frequency band of pulse interval. L-NAME treatment increased the LF band of systolic arterial pressure only in CTR without changes in MSG. Lipid peroxidation levels were higher in MSG and were attenuated after L-NAME. In endothelial cells, basal FI to DAF was higher in CTR than in MSG. In both groups, acetylcholine increased FI for DAF from basal. The FI baseline to DHE was higher in MSG than in CTR. Acetylcholine increased FI to DHE in the CTR group, but decreased in MSG animals. We suggest that reduced NO production and increased production of ROS may contribute to hypertension in obese MSG animals., (Copyright © 2014 the American Physiological Society.)

We aimed to examine the cardiovascular function by tonic and baroreflex alterations in obese rats induced by monosodium glutamate (MSG). Neonatal male Wistar rats were injected with MSG (4 mg/g body weight) or equimolar saline (control, C). At 90 days, all rats were anesthetized for catheterization of the femoral artery for mean arterial pressure (MAP) and heart rate (HR) recordings in the conscious state. After baseline, we performed IV treatment with hexamethonium (25 mg/kg), or atropine (1 mg/kg) or propranolol (3 mg/kg). We also performed the spectral analysis of heart rate variability (HRV) and baroreflex sensitivity. Baseline comparison showed that obese rats are hypertensive compared with control (C=110±2 mmHg; MSG=: 123±3 mmHg, P<0.05). After ganglionic blockade with hexamethonium the differences in MAP between control and obese rats disappeared. Beta adrenergic blockade with propranolol induced a greater decrease in heart rate compared with control. The analysis of HRV showed that obese rats have increased modulation by both components of the autonomic nervous system compared with control rats. The baroreflex gain showed increased sensitivity for the parasympathetic component in the obese rats (C=-2.41±0.25; MSG=-3.34±0.23 bpm/mmHg) compared with control. Our data suggest that both components of autonomic cardiac tonus and the parasympathetic component of the baroreflex sensitivity are increased in the MSG obese rat. It is possible that the parasympathetic alterations observed in these MSG obese rats may have originated from central areas of cardiovascular control., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The literature suggests that both obesity and hypertension are associated with increased sympathetic nerve activity. In the present study we evaluated the renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) in hyperadipose rats induced by neonatal administration of monosodium glutamate (MSG). Neonatal Wistar male rats were injected with MSG (4 mg/g body weight ID) or equimolar saline (control) for 5 days. At 90th day, all rats were anesthetized (urethane 1.4 g/kg) and prepared for MAP, HR and renal sympathetic nerve activity recordings. The anesthetized MSG rats presented baseline hypertension and increased baseline RSNA compared with control. Our results suggest the involvement of the renal sympathetic nervous system in the physiopathology of the MSG obesity., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

We evaluate the effects of chronic treatment with celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, on blood pressure (BP) and heart rate variability (HRV) in obese rats induced by neonatal monosodium glutamate (MSG). The animals were treated with celecoxib or saline for 30 days (from the 60th to the 90th day of age). On the 90th day, the MSG obesity induced an increase in the low-frequency (LF) component (CTR=5.69±18.30ms(2), MSG=38.49±6.27ms(2)) and a decrease in the high-frequency (HF) component of HRV (CTR=71.48±6.22ms(2), MSG=50.94±7.03ms(2)), which were unchanged by celecoxib treatment. We suggest that HRV in MSG obesity involves a greater sympathetic modulation not related with COX-2 products., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Aims: the purpose of the present work was to investigate the effect of cyclooxygenase-2 (COX-2) inhibition on the cardiovascular and inflammatory aspects promoted by monosodium glutamate (MSG)-induced obesity in rats., Main Methods: Neonatal Wistar male rats were injected with MSG (4 mg/g body weight ID) or equimolar saline (control). Treatment with celecoxib (50 mg/kg ip) or saline (0.9% NaCl ip) began at 60 days of age. At 90 days, all rats were anesthetized for catheterization of the femoral artery, and the mean arterial pressure (MAP) and heart rate (HR) were recorded once consciousness was regained., Key Findings: MSG obese rats were hypertensive (MAP=138±4 mm Hg) compared with controls (MAP=118±2 mm Hg). After treatment with celecoxib, the hypertension was attenuated (MAP=126±2 mm Hg) in obese rats without changes in HR. The retroperitoneal and periepididymal fat weighed more in obese rats (Obese: Retro=7.08±0.51, Peri=6.36±0.81, CONTROL: Retro=3.60±0.46; Peri=3.24±0.42), but celecoxib did not alter these parameters. Plasma nitric oxide levels were not different between groups. However, the level of plasma prostaglandins, the immunohistochemical staining of COX-2 in cardiac tissue and plasma lipoperoxidation were higher in obese rats, and celecoxib attenuated these parameters. MSG produced liver steatosis that was also attenuated following celecoxib treatment., Significance: Our data demonstrate an association between increased blood pressure and products of COX-2 in obese rats, suggesting a role for prostaglandins in the hypertensive and inflammatory aspects of MSG-induced obesity., (2010 Elsevier Inc. All rights reserved.)