Acute toxic effects of telmisartan in spontaneously hypertensive rats fed a high fructose diet

Title:

Acute toxic effects of telmisartan in spontaneously hypertensive rats fed a high fructose diet

Creator:

Šilhavý, J., Mlejnek, P. , Šimáková, M., Vaněčková, I., Behuliak, M. , Kuda, O., Sticová, E. , Jirsa, M. , and Pravenec , M.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:fc30f7c8-cae0-412f-8ff1-4f227685357a
uuid:fc30f7c8-cae0-412f-8ff1-4f227685357a

Subject:

telmisartan, spontaneously hypertensive rat, fructose, and toxic

Type:

model:article and TEXT

Format:

bez média and svazek

Description:

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.

Language:

English

Rights:

http://creativecommons.org/publicdomain/mark/1.0/
policy:public

Source:

Physiological research | 2018 Volume:67 | Number:6

Harvested from:

CDK

Metadata only:

false