Felodipine reduces cardiac expression of IL-18 and perivascular fibrosis in fructose-fed rats.
Metabolic syndrome is associated with accelerated macrovascular and microvascular coronary disease, cardiomyopathy, and elevated inflammatory status. To determine whether metabolic syndrome-associated elevation of the inflammatory cytokine interleukin-18 (IL-18) in serum and cardiac tissue, and its potential sequelae could be attenuated pharmacologically, we studied fructose-fed rats. The fructose-fed rats exhibited increases in systolic blood pressure (SBP), body weight, heart weight, left ventricular weight, and blood insulin. Serum IL-18 levels in these rats were also elevated significantly. These changes were significantly different compared to those in control rats. Perivascular fibrosis around coronary arterioles was evident in the fructose-fed rats, accompanied by a paralleled increase in IL-18 by immunohistochemical analysis and real time polymerase chain reaction. Felodipine attenuated the increased levels in serum IL-18 and cardiac IL-18 mRNA as well as coronary perivascular fibrosis. Thus, augmented IL-18 in serum and cardiac tissue in metabolic syndrome may contribute to the coronary perivascular fibrosis; felodipine administration can attenuate the inflammatory and fibrosis process.
Xing
Shan-Shan
SS
Department of Cardiology, QiLu Hospital, Shandong University, Jinan, China.
Tan
Hong-Wei
HW
Bi
Xiu-Ping
XP
Zhong
Ming
M
Zhang
Yun
Y
Zhang
Wei
W
D000821:Animal Feed; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D015736:Felodipine / Q000494:pharmacology* / Q000627:therapeutic use; D005355:Fibrosis / Q000188:drug therapy; D005632:Fructose / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D020382:Interleukin-18 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D011921:Rats, Inbred WKY
D000959:Antihypertensive Agents; D020382:Interleukin-18; D005632:Fructose; D015736:Felodipine