Effects of lignans extracted from Eucommia ulmoides and aldose reductase inhibitor epalrestat on hypertensive vascular remodeling.
OBJECTIVE
To investigate the effects of lignans extracted from Eucommia ulmoides and epalrestat on vascular remodeling in spontaneously hypertensive rats.


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.
Gu
Juan
J
Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, PR China.
Wang
Jun-Jie
JJ
Yan
Jin
J
Cui
Chang-Fu
CF
Wu
Wei-Hua
WH
Li
Ling
L
Wang
Zhen-Shan
ZS
Yu
Min
M
Gao
Na
N
Liu
Li
L
Ouyang
Dong-Sheng
DS
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D031283:Eucommiaceae; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000201:enzymology / Q000473:pathology; D024301:Plant Bark; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D053778:Thiazolidines / Q000494:pharmacology*
D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D017705:Lignans; D053778:Thiazolidines; C038131:epalrestat; D012236:Rhodanine; D002216:Captopril; D000449:Aldehyde Reductase