Pentoxifylline alleviates hypertension in metabolic syndrome: effect on low-grade inflammation and angiotensin system

Abstract

Introduction and objective: Pentoxifylline is a well-tolerated drug used in treatment of vascular insufficiency. We previously showed that pentoxifylline protects from impairment in vascular reactivity in cases of metabolic syndrome. The aim of this study was to investigate the protective effect of pentoxifylline against hypertension in metabolic syndrome rats.

Methods: Metabolic syndrome was induced by feeding rats a high-fructose, high-fat and high-salt diet for 12 weeks. Pentoxifylline was administered daily (30 mg kg(-1)) during the last 4 weeks of the study, before blood pressure parameters were assessed at the end of study. In addition, serum levels of glucose, fructosamine, insulin, tumor necrosis factor alpha, adiponectin, and lipid profile parameters were determined. Aortic protein levels of angiotensin II and angiotensin receptor 1 were assessed by immunofluorescence.

Results: Pentoxifylline administration prevented excessive weight gain but did not affect hyperinsulinemia or hypertriglyceridemia seen in metabolic syndrome animals. In addition, pentoxifylline prevented the elevations in mean blood pressure associated with metabolic syndrome. Particularly, pentoxifylline prevented elevations in systolic, diastolic, and notch blood pressure; however, elevation in pulse blood pressure was not affected. Further, pentoxifylline alleviated the low-grade inflammation associated with metabolic syndrome, as reflected by the significantly lower serum tumor necrosis factor α and higher serum adiponectin levels metabolic syndrome animals treated with pentoxifylline. Also, pentoxifylline inhibited elevated expression of angiotensin receptor 1 in aortic tissue of metabolic syndrome animals.

Conclusion: Pentoxifylline directly alleviated hypertension in metabolic syndrome rats, at least in part, via amelioration of low-grade inflammation and inhibition of angiotensin system.

Keywords: Hypertension; Insulin resistance; Pentoxifylline; Vascular.