Bezafibrate, an anti-hypertriglyceridemic drug, attenuates vascular hyperresponsiveness and elevated blood pressure in fructose-induced hypertensive rats.
A high fructose diet induces hypertension, hyperinsulinemia - insulin resistance, and hypertriglyceridemia (syndrome X). In this study, we investigated the role of an abnormal lipid profile in mediating fructose-induced hypertension. We hypothesized that bezafibrate, a lipid-lowering drug, would reduce elevated blood pressure and inhibit increased vascular reactivity in fructose-fed rats. Male rats were placed on four different diets: group 1 was fed standard chow (n = 6); group 2 was fed 60% fructose (n = 5); group 3 was fed fructose plus bezafibrate (30 mg x kg(-1) x day(-1); drinking water; n = 5); and group 4 was fed standard chow plus bezafibrate (n = 6). In addition, the direct effects of very low density lipoprotein (VLDL) on vascular reactivity were examined. Bezafibrate treatment lowered blood pressure, free fatty acids, and triglycerides in the fructose-fed group, suggesting that lipid abnormalities play a role in the elevation of blood pressure in the fructose-induced hypertensive rat. Aortae from fructose-fed rats were hyperresponsive to the calcium channel agonist Bay K 8644, which was normalized with bezafibrate treatment. Incubation of aortae in a VLDL medium resulted in increased responsiveness to Bay K 8644, lending further support to lipid abnormalities altering vascular reactivity. An altered lipid profile evidenced by elevated triglycerides and free fatty acids is causally related to the development of high blood pressure and increased vascular reactivity in the fructose-induced hypertensive rat.
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Department of Physiology, University of Michigan, Ann Arbor 48109-0622, USA.
Webb
R C
RC
Richey
J M
JM
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001629:Bezafibrate / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002120:Calcium Channel Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000494:pharmacology; D006946:Hyperinsulinism / Q000139:chemically induced; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D015228:Hypertriglyceridemia / Q000139:chemically induced / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008079:Lipoproteins, VLDL / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D002120:Calcium Channel Agonists; D000960:Hypolipidemic Agents; D008079:Lipoproteins, VLDL; D005632:Fructose; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D001629:Bezafibrate