Pentoxifylline Ameliorates Cardiac Fibrosis, Pathological Hypertrophy, and Cardiac Dysfunction in Angiotensin II-induced Hypertensive Rats.
Inflammation induces cardiac fibrosis and hypertrophy in multiple cardiovascular diseases, contributing to cardiac dysfunction. We tested the hypothesis that pentoxifylline (PTX), a phosphodiesterase inhibitor with anti-inflammatory property, would attenuate cardiac fibrosis and hypertrophy, and prevent cardiac dysfunction in angiotensin (ANG) II-induced hypertensive rats. Sprague-Dawley rats were divided into control and ANG II-infused groups treated with or without PTX for 2 weeks. PTX had no effect on ANG II-induced hypertension, but significantly attenuated cardiac fibrosis and hypertrophy, and ameliorated cardiac dysfunction in ANG II-induced hypertensive rats. In addition, ANG II-induced increase in circulating and cardiac proinflammatory cytokines were attenuated by PTX, which reduced cardiac nuclear factor-kappa B activity. Furthermore, PTX decreased cardiac expression of genetic markers important for fibrosis, hypertrophy, and endothelial dysfunction, and reduced migration and infiltration of macrophages. In contrast, PTX had no effects on the above parameters in control rats. The findings suggest that PTX ameliorates cardiac fibrosis, pathological hypertrophy, and cardiac dysfunction by suppressing inflammatory responses in angiotensin II-induced hypertension, and that these benefits were independent of the blood pressure lowering effect. The PTX by its anti-inflammatory property may be a potential therapeutic option for the prevention of cardiac remodeling and dysfunction in ANG II-induced hypertension.
*Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan City, China; †Department of Anesthesiology, Jinan Maternity and Childcare Hospital, Jinan City, China; ‡Department of Anesthesiology, Second People's Hospital of Liaocheng, Liaocheng City, China; and §Department of Emergency, Chest Pain Center, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, and Key Laboratory of Cardiovascular Remodeling & Function Research, Chinese Ministry of Education & Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China.
Xiyan
X
Zhang
Fanqing
F
Meng
Jie
J
Song
Li
L
Zhang
Jiali
J
Wang
Dongliang
D
Li
Liang
L
Li
Ping
P
Dong
Bo
B
Yang
Yuguo
Y
Chen
D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy* / Q000378:metabolism; D005355:Fibrosis; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D018836:Inflammation Mediators; D010726:Phosphodiesterase Inhibitors; D000804:Angiotensin II; D010431:Pentoxifylline