scholarly journals Acute Toxic Effects of Telmisartan in Spontaneously Hypertensive Rats Fed a High Fructose Diet

2018 ◽  
pp. 851-856
Author(s):  
J. ŠILHAVÝ ◽  
P. MLEJNEK ◽  
M. ŠIMÁKOVÁ ◽  
I. VANĚČKOVÁ ◽  
M. BEHULIAK ◽  
...  
Keyword(s):  
Body Weight ◽  
Spontaneously Hypertensive Rats ◽  
Toxic Effects ◽  
Metabolic Effects ◽  
Brown Norway ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
High Fructose Diet ◽  
High Fructose ◽  
Acute Toxic

Telmisartan is an angiotensin receptor blocker (ARB) and a selective peroxisome proliferator activated receptor gamma (PPARG) modulator. Recently, we tested metabolic effects of telmisartan (5 mg/kg body weight) in spontaneously hypertensive rats (SHR) fed a diet containing 60 % fructose, a widely used model of the metabolic syndrome. Surprisingly, we observed acute toxic effects of telmisartan. Rats lost body weight rapidly and died within 2 to 3 weeks due to bleeding into the upper gastrointestinal tract. SHR fed a high fructose diet and treated with telmisartan exhibited rapid decrease in blood pressure when compared to the SHR fed a high fructose diet and treated with valsartan. Concentrations of both unconjugated telmisartan and telmisartan glucuronide in the liver of SHR rats fed a high fructose diet were approximately 4 fold higher when compared to Brown Norway (BN) rats fed the same diet. Plasma concentrations of unconjugated telmisartan in the SHR were about 5 fold higher when compared to BN rats while plasma levels of telmisartan glucuronide were similar between the strains. Testing of other rat strains, diets, and the ARB valsartan showed that toxic effects of telmisartan in combination with high fructose diet are specific for the SHR. These results are consistent with the possibility that in some circumstances, SHR are predisposed to telmisartan toxicity possibly because of a genetically determined disturbance in telmisartan metabolism.

scholarly journals Hepatotoxic Effects of Fenofibrate in Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein

2016 ◽  
pp. 891-899 ◽  
Author(s):  
V. ŠKOP ◽  
J. TRNOVSKÁ ◽  
O. OLIYARNYK ◽  
I. MARKOVÁ ◽  
H. MALÍNSKÁ ◽  
...  
Keyword(s):  
Body Weight ◽  
Spontaneously Hypertensive Rats ◽  
Hdl Cholesterol ◽  
Metabolic Effects ◽  
C Reactive Protein ◽  
Hypertensive Rats ◽  
Serum Triglycerides ◽  
Spontaneously Hypertensive ◽  
Reactive Protein ◽  
Anti Inflammatory

Dyslipidemia and inflammation play an important role in the pathogenesis of cardiovascular and liver disease. Fenofibrate has a well-known efficacy to reduce cholesterol and triglycerides. Combination with statins can ameliorate hypolipidemic and anti-inflammatory effects of fibrates. In the current study, we tested the anti-inflammatory and metabolic effects of fenofibrate alone and in combination with rosuvastatin in a model of inflammation and metabolic syndrome, using spontaneously hypertensive rats expressing the human C-reactive protein transgene (SHR-CRP transgenic rats). SHR-CRP rats treated with fenofibrate alone (100 mg/kg body weight) or in combination with rosuvastatin (20 mg/kg body weight) vs. SHR-CRP untreated controls showed increased levels of proinflammatory marker IL6, increased concentrations of ALT, AST and ALP, increased oxidative stress in the liver and necrotic changes of the liver. In addition, SHR-CRP rats treated with fenofibrate, or with fenofibrate combined with rosuvastatin vs. untreated controls, exhibited increased serum triglycerides and reduced HDL cholesterol, as well as reduced hepatic triglyceride, cholesterol and glycogen concentrations. These findings suggest that in the presence of high levels of human CRP, fenofibrate can induce liver damage even in combination with rosuvastatin. Accordingly, these results caution against the possible hepatotoxic effects of fenofibrate in patients with high levels of CRP.

The Tnfα-Gene Locus and Body-Weight Response to a High-Fat Diet in Spontaneously Hypertensive Rats

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 728-728
Author(s):  
Zdenka Pausova ◽  
Pavel Hamet ◽  
Michal Pravenec ◽  
Vladimir Kren
Keyword(s):  
Body Weight ◽  
Spontaneously Hypertensive Rats ◽  
Gene Locus ◽  
Dietary Intervention ◽  
Brown Norway ◽  
High Fat ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Linkage And Association Analysis ◽  
Main Factors

P192 Objective: Using linkage and association analysis, we have previously demonstrated that the TNFα−gene locus contributes to the determination of obesity and obesity-associated hypertension in hypertensive pedigrees of French-Canadian origin. The aim of the present study was to investigate whether the TNFα-gene locus is involved in the regulation of body weight (BW) response to a high-fat (HF) diet in spontaneously hypertensive rats (SHR). Methods: The effect of the TNFα−gene locus was investigated with the use of a congenic strain, SHR.1N, which differs from SHR by a segment of chromosome 20 originating from the normotensive Brown Norway rat and containing the TNFα gene. Sixteen-week-old SHR and SHR.1N were placed on either a normal (N; 5P14, Prolab 2500) or HF (F3282, Bio-Serv) diet for 12 weeks. BW was measured weekly. The BW response to the dietary intervention was assessed by three-way ANOVA with Strain (SHR and SHR.1N), Diet(N and HF) and Time (11 time points) as the main factors. Results: During the 12-week period, SHR (n = 16) and SHR.1N (n = 17) fed the HF diet increased their BW by 31% and 42%, respectively; and SHR (n = 13) and SHR.1N (n = 13) fed the N diet augmented their BW by only 18% and 19%, respectively. ANOVA demonstrated a significant effect of all three main factors, Strain (F 1,55 = 6.86, p = 0.01), Diet (F 1,55 = 85.69, p = 0.0001), and Time (F 10,550 = 236.12, p = 0.0001), and a significant three-way interaction between Strain, Diet and Time (F 10,550 = 2.58, p = 0.04). Subsequent two-way ANOVA showed that the effect of Strain and Time-Strain interaction was significant in rats fed the HF diet (F 1,31 = 11.01, p = 0.002; F 10,310 = 6.7, p = 0.0001, respectively), but not in rats fed the N diet (F 1,24 = 0.06, p = 0.8; F 10,240 = 1.31, p = 0.3, respectively). Summary and Conclusion: During feeding with the HF diet, both SHR and SHR.1N increased their BW, but the increase was greater in SHR.1N. These results suggest that a gene(s) exist(s) within the differential chromosomal segment of SHR.1N, which is involved in regulation of the BW response to the HF diet. Considering the known functional properties of TNFα, the TNFα gene is the best candidate within the segment.

Effect of chlorothiazide on serial measurements of exchangeable sodium and blood pressure in spontaneously hypertensive rats

1985 ◽  
Vol 69 (5) ◽  
pp. 511-515 ◽  
Author(s):  
P. J. O. Manhem ◽  
S. A. Clark ◽  
W. B. Brown ◽  
G. D. Murray ◽  
J. I. S. Robertson
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Spontaneously Hypertensive Rats ◽  
Tap Water ◽  
Treated Group ◽  
Temporal Association ◽  
Control Group ◽  
Exchangeable Sodium ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

1. Chlorothiazide (100 mg/kg body weight) was given by gavage daily to spontaneously hypertensive rats for 4 weeks. Another group of spontaneously hypertensive rats was given only tap water and served as control. 2. Measurements of total exchangeable sodium, blood pressure and weight were performed for 2 weeks before and for 4 weeks during treatment. 3. Before treatment, exchangeable sodium, blood pressure and weight were similar in the two groups of rats. 4. Chlorothiazide significantly attenuated the blood pressure increase in spontaneously hypertensive rats, the effect being most marked during the first 2 1/2 weeks of treatment and less thereafter. 5. Rats in the chlorothiazide-treated group gained weight more slowly than did those of the control group. 6. Exchangeable sodium, expressed as mmol/kg body weight, did not differ significantly between the two groups at any stage. 7. When exchangeable sodium was expressed as mmol/rat, there was a more gradual rise in the chlorothiazide-treated animals, in accordance with their slower gain in weight. 8. There was no temporal association between the antihypertensive effect of chlorothiazide and changes in exchangeable sodium. 9. Thus whereas chlorothiazide treatment of spontaneously hypertensive rats slows the increase of both weight and exchangeable sodium, other mechanisms are apparently responsible for the antihypertensive action of the drug.

Metabolic effects of telmisartan in spontaneously hypertensive rats

2006 ◽  
Vol 373 (4) ◽  
pp. 264-270 ◽  
Author(s):  
Yong-Qi Li ◽  
Hui Ji ◽  
Yi-Hua Zhang ◽  
Da-Yong Ding ◽  
Xiao-Lei Ye
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Metabolic Effects ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Lack of beneficial metabolic effects of quercetin in adult spontaneously hypertensive rats

2010 ◽  
Vol 627 (1-3) ◽  
pp. 242-250 ◽  
Author(s):  
Miguel Romero ◽  
Rosario Jiménez ◽  
Belén Hurtado ◽  
Juan Manuel Moreno ◽  
Isabel Rodríguez-Gómez ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Metabolic Effects ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Hemodynamic and Metabolic Effects of Hypomagnesemia in Spontaneously Hypertensive Rats

Cardiology ◽  
1988 ◽  
Vol 75 (2) ◽  
pp. 81-89 ◽  
Author(s):  
Steven G. Chrysant ◽  
Louis Ganousis ◽  
Catherine Chrysant
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Metabolic Effects ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive
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