Metabolic effects of telmisartan in spontaneously hypertensive rats.
The favorable metabolic effects of telmisartan are supposedly related to the changes in carbohydrate and lipid metabolism driven by peroxisome proliferators-activated receptor-gamma (PPARgamma). The fatty acid translocase CD36 is one of the PPARgamma targets that mediate these actions. We studied the metabolic effects of telmisartan in the NIH-derived strain of spontaneously hypertensive rats (SHR/NIH), which harbors a deletion mutation in CD36, in comparison to the original SHRs (SHR/Izm), which express wild-type CD36. In SHR/Izm, administration of telmisartan was associated with significantly lower serum levels of free fatty acids (42%), triglycerides (29%), glucose (11%), insulin (31%), and lower hepatic triglyceride (17%) levels, as well as larger epididymal fat pads (1.19-fold) than in SHR/NIH. Additionally, insulin-stimulated glucose incorporation into epididymal fat tissues was significantly augmented in SHR/Izm (1.33-fold) compared with SHR/NIH. In the epididymal fat pads of SHR/Izm treated with telmisartan, CD36 mRNA transcript (1.55-fold) and protein expression (1.37-fold) were also significantly enhanced. However, after 4 weeks of treatment with telmisartan, in SHR/NIH only serum free fatty acid levels were slightly reduced (20%). Overall, these results showed marked discrepancies in the metabolic actions of telmisartan in SHR/Izm and SHR/NIH and further supported the involvement of CD36 in the actions of this drug, suggesting that this pharmacogenetic interaction may be of particular importance in CD36-deficient patients.
Li
Yong-Qi
YQ
Department of Pharmacology, China Pharmaceutical University, 24 Tong Jia Xiang, 210009 Nangjing, People's Republic of China.
Ji
Hui
H
Zhang
Yi-Hua
YH
Ding
Da-Yong
DY
Ye
Xiao-Lei
XL
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000737:chemistry; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry; D051381:Rats; D011918:Rats, Inbred SHR; D000077333:Telmisartan; D014280:Triglycerides / Q000032:analysis
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D018955:CD36 Antigens; D014280:Triglycerides; D005947:Glucose; D000077333:Telmisartan