Effects of lignans extracted from Eucommia ulmoides and aldose reductase inhibitor epalrestat on hypertensive vascular remodeling

Abstract

Aim of the study: To investigate the effects of lignans extracted from Eucommia ulmoides and epalrestat on vascular remodeling in spontaneously hypertensive rats.

Materials and methods: Ten-week-old male spontaneously hypertensive rats were randomly divided into 3 groups (12 rats each group), and treated orally with 100 mg/kg/d of captopril (an angiotensin-converting enzyme inhibitor), 100 mg/kg/d of epalrestat (an aldose reductase inhibitor) and 300 mg/kg/d of lignans by gavage daily for 16 weeks, respectively. Sex-, age-, and number-matched spontaneously hypertensive rats and normotensive Wistar Kyoto rats, were treated with distilled water (vehicle) as controls. The rats were weighed weekly. Mean arterial blood pressure and heart rate were measured periodically by non-invasive blood pressure monitoring. They were sacrificed at the end of experiment (26-week-old). Superior mesenteric artery and aorta were isolated for determination of histomorphometry and the expression of aldose reductase by immunohistochemistry.

Results: Captopril and lignans, but not epalrestat, decreased mean arterial blood pressure in spontaneously hypertensive rats. Vascular remodeling was improved in all three treated groups by histomorphometry.

Conclusions: Both lignans and epalrestat reversed hypertensive vascular remodeling. Aldose reductase played a vital role in the pathologic process of hypertensive vascular remodeling rather than elevation of blood pressure. These data suggested that aldose reductase could be a new therapeutic target for the treatment of cardiovascular diseases.