Glomerulosclerosis in the diet-induced obesity model correlates with sensitivity to nitric oxide inhibition but not glomerular hyperfiltration or hypertrophy

The diet-induced obesity (DIO) model is frequently used to examine the pathogenesis of obesity-related pathologies; however, only minimal glomerulosclerosis (GS) has been reported after 3 mo. We investigated if GS develops over longer periods of DIO and examined the potential role of hemodynamic mechanisms in its pathogenesis. Eight-week-old male obesity-prone (OP) and obesity-resistant (OR) rats (Charles River) were administered a moderately high-fat diet for 5 mo. Radiotelemetrically measured blood pressure, proteinuria, and GS were assessed. OP ( n = 10) rats developed modest hypertension (142 ± 3 vs. 128 ± 2 mmHg, P < 0.05) and substantial levels of proteinuria (63 ± 12 vs. 12 ± 1 mg/day, P < 0.05) and GS (7.7 ± 1.4% vs. 0.4 ± 0.2%) compared with OR rats ( n = 8). Potential hemodynamic mechanisms of renal injury were assessed in additional groups of OP and OR rats fed a moderately high-fat diet for 3 mo. Kidney weight (4.3 ± 0.2 vs. 4.3 ± 0.1 g), glomerular filtration rate (3.3 ± 0.3 vs. 3.1 ± 0.1 ml/min), and glomerular volume (1.9 ± 0.1 vs. 2.0 ± 0.1 μm3 × 10−6) were similar between OP ( n = 6) and OR ( n = 9) rats. Renal blood flow autoregulation was preserved in both OP ( n = 7) and OR ( n = 7) rats. In contrast, Nω-nitro-l-arginine methyl ester (l-NAME) administration in conscious, chronically instrumented OP ( n = 11) rats resulted in 15% and 39% increases in blood pressure and renal vascular resistance, respectively, and a 16% decrease in renal blood flow. Minimal effects of l-NAME were seen in OR ( n = 9) rats. In summary, DIO-associated GS is preceded by an increased hemodynamic sensitivity to l-NAME but not renal hypertrophy or hyperfiltration.

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Telmisartan prevents high-fat diet-induced neurovascular impairments and reduces anxiety-like behavior

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x211003497 ◽

2021 ◽

pp. 0271678X2110034

Author(s):

Gianna Huber ◽

Mikolaj Ogrodnik ◽

Jan Wenzel ◽

Ines Stölting ◽

Lukas Huber ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

High Fat Diet ◽

Neurovascular Unit ◽

Laser Speckle ◽

Angiotensin Ii Receptor ◽

High Fat ◽

Diet Induced Obesity ◽

Whisker Pad ◽

Receptor Blockers

Angiotensin II receptor blockers (telmisartan) prevent rodents from diet-induced obesity and improve their metabolic status. Hyperglycemia and obesity are associated with reduced cerebral blood flow and neurovascular uncoupling which may lead to behavioral deficits. We wanted to know whether a treatment with telmisartan prevents these changes in obesity. We put young mice on high-fat diet and simultaneously treated them with telmisartan. At the end of treatment, we performed laser speckle imaging and magnetic resonance imaging to assess the effect on neurovascular coupling and cerebral blood flow. Different behavioral tests were used to investigate cognitive function. Mice developed diet-induced obesity and after 16, not 8 weeks of high-fat diet, however, the response to whisker pad stimulation was about 30% lower in obese compared to lean mice. Simultaneous telmisartan treatment increased the response again by 10% compared to obese mice. Moreover, telmisartan treatment normalized high-fat diet-induced reduction of cerebral blood flow and prevented a diet-induced anxiety-like behavior. In addition to that, telmisartan affects cellular senescence and string vessel formation in obesity. We conclude, that telmisartan protects against neurovascular unit impairments in a diet-induced obesity setting and may play a role in preventing obesity related cognitive deficits in Alzheimer’s disease.

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Adiponectin knockout accentuates high fat diet-induced obesity and cardiac dysfunction: Role of autophagy

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ◽

10.1016/j.bbadis.2013.03.013 ◽

2013 ◽

Vol 1832 (8) ◽

pp. 1136-1148 ◽

Cited By ~ 89

Author(s):

Rui Guo ◽

Yingmei Zhang ◽

Subat Turdi ◽

Jun Ren

Keyword(s):

Cardiac Dysfunction ◽

High Fat Diet ◽

High Fat ◽

Diet Induced Obesity

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Angiotensin 1-7 Administration Increases Renal Blood Flow in the Absence of Bradykinin B2 Receptor in Ovariectomized Estradiol Treated Rats: The Role of Mas Receptor

ACTA MEDICA IRANICA ◽

10.18502/acta.v57i2.1764 ◽

2019 ◽

Author(s):

Shadan Saberi ◽

Aghdas Dehghani ◽

Mehdi Nematbakhsh

Keyword(s):

Blood Flow ◽

Renal Blood Flow ◽

Ovariectomized Rats ◽

Vehicle Group ◽

Estradiol Valerate ◽

Bradykinin B2 Receptor ◽

Hoe 140 ◽

Group 2 ◽

Renal Vascular

Abstract- Renin angiotensin (RAS), kallikrein kinin (KKS), and sex hormonal systems demonstrate a complex contribution in kidney circulation. This study was designed to investigate the role of angiotensin 1-7 (Ang 1-7) receptor (MasR) and of bradykinin B2 receptor (B2R) in renal blood flow (RBF) response to Ang 1-7 infusion in ovariectomized estradiol treated rats. The ovariectomized rats received intramuscular vehicle (group 1, OV) or estradiol valerate (500 µg/Kg/week) (group 2, OVE) for two weeks. Then each group was divided into two subgroups subjected to receive B2R antagonist (HOE-140, subgroup A), or MasR antagonist (A779) plus HOE-140 (subgroup B). RBF and renal vascular resistance (RVR) responses to graded Ang 1-7 infusion were determined. In condition of B2R alone blocking, RBF response to Ang 1-7 in OVE group was significantly greater than that of OV group (P=0.05), however this response difference was failed by co-blockades of MasR and B2R. Estradiol could promote RBF response to graded Ang 1-7 infusion in the absence of B2R alone, however when both receptors (MasR and B2R) were blocked the role of estradiol was limited.

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The protective role of the opioid antagonist LY255582 in the management of high fat diet-induced obesity in adult male albino rats

Endocrine Regulations ◽

10.4149/endo_2015_04_198 ◽

2015 ◽

Vol 49 (04) ◽

pp. 198-205 ◽

Cited By ~ 1

Author(s):

I. Y. Ibrahim ◽

H. M. Ibrahim ◽

N. M. Aziz ◽

D. M. Rahman

Keyword(s):

Adult Male ◽

High Fat Diet ◽

Protective Role ◽

Opioid Antagonist ◽

Albino Rats ◽

High Fat ◽

Diet Induced Obesity

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Ameliorative effect of selegiline in high fat diet induced obesity rat model: Possible role of dopaminergic pathway

Obesity Medicine ◽

10.1016/j.obmed.2020.100301 ◽

2020 ◽

Vol 20 ◽

pp. 100301

Author(s):

Amit Goyal ◽

Ankita Sharma ◽

Deepika Sharma ◽

Tapan Behl ◽

Anjoo Kamboj ◽

...

Keyword(s):

Rat Model ◽

High Fat Diet ◽

High Fat ◽

Diet Induced Obesity ◽

Dopaminergic Pathway ◽

Ameliorative Effect

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Renal vasodilatation after inhibition of renin or converting enzyme in marmoset

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1986.251.5.h897 ◽

1986 ◽

Vol 251 (5) ◽

pp. H897-H902

Author(s):

D. Neisius ◽

J. M. Wood ◽

K. G. Hofbauer

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Angiotensin Ii ◽

Renal Blood Flow ◽

Vascular Resistance ◽

Enzyme Inhibitor ◽

Renal Vascular Resistance ◽

Converting Enzyme ◽

Renin Inhibition ◽

Renal Vascular

The relative importance of angiotensin II for the renal vasodilatory response after converting-enzyme inhibition was evaluated by a comparison of the effects of converting-enzyme and renin inhibition on renal vascular resistance. Renal, mesenteric, and hindquarter blood flows were measured with chronically implanted ultrasonic-pulsed Doppler flow probes in conscious, mildly volume-depleted marmosets after administration of a converting-enzyme inhibitor (enalaprilat, 2 mg/kg iv), a synthetic renin inhibitor (CGP 29,287, 1 mg/kg iv), or a renin-inhibitory monoclonal antibody (R-3-36-16, 0.1 mg/kg iv). Enalaprilat reduced blood pressure (-16 +/- 4 mmHg, n = 6) and induced a selective increase in renal blood flow (27 +/- 8%, n = 6). CGP 29,287 and R-3-36-16 induced comparable reductions in blood pressure (-16 +/- 4 mmHg, n = 6 and -20 +/- 4 mmHg, n = 5, respectively) and selective increases in renal blood flow (36 +/- 12%, n = 6 and 34 +/- 16%, n = 4, respectively). The decrease in renal vascular resistance was of similar magnitude for all of the inhibitors (enalaprilat -28 +/- 3%, CGP 29,287 -32 +/- 6%; and R-3-36-16 -33 +/- 7%). These results indicate that the renal vasodilatation induced after converting-enzyme or renin inhibition is mainly due to decreased formation of angiotensin II.

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Role of Mas Receptor Antagonist A799 in Renal Blood Flow Response to Ang 1-7 after Bradykinin Administration in Ovariectomized Estradiol-Treated Rats

Advances in Pharmacological Sciences ◽

10.1155/2015/801053 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Aghdas Dehghani ◽

Shadan Saberi ◽

Mehdi Nematbakhsh

Keyword(s):

Blood Flow ◽

Renal Blood Flow ◽

Wistar Rats ◽

Group Versus ◽

Dependent Manner ◽

Mas Receptor ◽

Flow Response ◽

Renal Vascular ◽

Dose Dependent

Background. The accompanied role of Mas receptor (MasR), bradykinin (BK), and female sex hormone on renal blood flow (RBF) response to angiotensin 1-7 is not well defined. We investigated the role of MasR antagonist (A779) and BK on RBF response to Ang 1-7 infusion in ovariectomized estradiol-treated rats.Methods. Ovariectomized Wistar rats received estradiol (OVE) or vehicle (OV) for two weeks. Catheterized animals were subjected to BK and A799 infusion and mean arterial pressure (MAP), RBF, and renal vascular resistance (RVR) responses to Ang 1-7 (0, 100, and 300 ng kg−1 min−1) were determined.Results. Percentage change of RBF (%RBF) in response to Ang1-7 infusion increased in a dose-dependent manner. In the presence of BK, when MasR was not blocked, %RBF response to Ang 1-7 in OVE group was greater than OV group significantly (P<0.05). Infusion of 300 ng kg−1 min−1Ang 1-7 increased RBF by6.9±1.9% in OVE group versus0.9±1.8% in OV group. However when MasR was blocked, %RBF response to Ang 1-7 in OV group was greater than OVE group insignificantly.Conclusion. Coadministration of BK and A779 compared to BK alone increased RBF response to Ang 1-7 in vehicle treated rats. Such observation was not seen in estradiol treated rats.

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Hypertrophic cardiomyopathy in high-fat diet-induced obesity: role of suppression of forkhead transcription factor and atrophy gene transcription

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00319.2008 ◽

2008 ◽

Vol 295 (3) ◽

pp. H1206-H1215 ◽

Cited By ~ 72

Author(s):

Cindy X. Fang ◽

Feng Dong ◽

D. Paul Thomas ◽

Heng Ma ◽

Leilei He ◽

...

Keyword(s):

Transcription Factor ◽

Palmitic Acid ◽

High Fat Diet ◽

Weight Control ◽

Dominant Negative ◽

High Fat ◽

Forkhead Transcription Factor ◽

Diet Induced Obesity ◽

Intracellular Ca

Cellular hypertrophy is regulated by coordinated pro- and antigrowth machineries. Foxo transcription factors initiate an atrophy-related gene program to counter hypertrophic growth. This study was designed to evaluate the role of Akt, the forkhead transcription factor Foxo3a, and atrophy genes muscle-specific RING finger (MuRF)-1 and atrogin-1 in cardiac hypertrophy and contractile dysfunction associated with high-fat diet-induced obesity. Mice were fed a low- or high-fat diet for 6 mo along with a food-restricted high-fat weight control group. Echocardiography revealed decreased fractional shortening and increased end-systolic diameter and cardiac hypertrophy in high-fat obese but not in weight control mice. Cardiomyocytes from high-fat obese but not from weight control mice displayed contractile and intracellular Ca2+ defects including depressed maximal velocity of shortening/relengthening, prolonged duration of shortening/relengthening, and reduced intracellular Ca2+ rise and clearance. Caspase activities were greater in high-fat obese but not in weight control mouse hearts. Western blot analysis revealed enhanced basal Akt and Foxo3a phosphorylation and reduced insulin-stimulated phosphorylation of Akt and Foxo3a without changes in total protein expression of Akt and Foxo3a in high-fat obese hearts. RT-PCR and immunoblotting results displayed reduced levels of the atrogens atrogin-1 and MuRF-1, the upregulated hypertrophic markers GATA4 and ciliary neurotrophic factor receptor-α, as well as the unchanged calcineurin and proteasome ubiquitin in high-fat obese mouse hearts. Transfection of H9C2 myoblast cells with dominant-negative Foxo3a adenovirus mimicked palmitic acid (0.8 mM for 24 h)-induced GATA4 upregulation without an additive effect. Dominant-negative Foxo3a-induced upregulation of pAkt and repression of phosphatase and tensin homologue were abrogated by palmitic acid. These results suggest a cardiac hypertrophic response in high-fat diet-associated obesity at least in part through inactivation of Foxo3a by the Akt pathway.

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