endothelin-1 and morin

High fructose (HF) feeding induces a moderate increase in blood pressure in rats, which is associated with insulin resistance, hyperinsulinemia, and hypertriglyceridemia. In the present study, we examined the chronic effect of morin, a flavonoid isolated from medicinal plants, on blood pressure, lipid profiles, and serum insulin and glucose in HF-induced hypertensive rats. Rats were divided into control group and HF-fed group during the first three weeks of experiments. Then, rats were further divided into four groups and treated for 4 more weeks as follows: 1) control group; 2) morin-treated (intraperitoneal 5 mg/kg/d) control group; 3) HF-fed group; 4) morin-treated, HF-fed group (n=8, each group). Morin-treated HF-fed group showed lower systolic blood pressure (SBP) (132.0+/-2.5 mmHg vs. 142.8+/-2.2 mmHg, p<0.05), lower serum insulin level (1.21+/-0.27 vs. 2.73+/-0.30 microIU/dl, p<0.05), and lower plasma triglycerides (47.8+/-5.0 vs. 65.5+/-5.0 mg/dl, p<0.05) than those of HF-fed group. Morin treatment also suppressed mRNA expression of endothelin-1 (ET-1) in the thoracic aorta from HF-induced hypertensive rats. Moreover, decreased renal sodium excretion in HF-induced hypertensive rats was ameliorated by morin treatment. In conclusion, the results of this study demonstrate that morin has an anti-hypertensive effect in HF-induced hypertensive rats. This effect of morin may be associated with the suppression of serum insulin and plasma triglyceride level, with the down-regulation of ET-1 in the thoracic aorta, and with the partial amelioration of renal dysfunctions in HF-induced hypertensive rats.

Topics: Animals; Antihypertensive Agents; Aorta; Blood Glucose; Blood Pressure; Cholesterol; Endothelin-1; Flavonoids; Fructose; Hypertension; Injections, Intraperitoneal; Insulin; Kidney; Male; Phytotherapy; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors; Triglycerides

Reactive oxygen species (ROS) play an important role in the damage of vascular endothelium during atherogenesis and impaired endothelium-dependent vasorelaxation. We have studied the effect of two ROS generators (H2O2 and menadione) and one of the most potent antioxidants (morin) on the double immunofluorescent staining of endothelial cells (EC) from both Watanabe Heritable Hyperlipidemic (WHHL) and New Zealand White (NZW) rabbits in primary cultures using antibodies against endothelin-1 (ET-1), endothelial (eNOS), and inducible nitric oxide synthase (iNOS). In aortic EC from normal rabbits, ROS decreased the immunoreactivity of eNOS and ET-1 and this effect was significantly reversed by morin. In atherosclerotic rabbits, ROS had the same effect on the immunoreactivity of eNOS and ET-1 but also induced the expression of iNOS immunoreactivity. In general, the cells from WHHL rabbits were less sensitive to the protective effects of morin and more sensitive to the effects of ROS. It thus appears that the protective effect of morin may be due to neutralization of ROS and may be considered for the treatment of early stages of atherosclerosis, before macroscopic lesions have occurred.

Topics: Animals; Antioxidants; Aorta; Cells, Cultured; Endothelin-1; Endothelium, Vascular; Flavonoids; Hyperlipidemias; Immunohistochemistry; Male; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Rabbits; Reactive Oxygen Species; Vitamin K