Bezafibrate, an anti-hypertriglyceridemic drug, attenuates vascular hyperresponsiveness and elevated blood pressure in fructose-induced hypertensive rats

Xiaochen Si, R Clinton Webb, Joyce M. Richey

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18 Citations (Scopus)

Abstract

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 · kg-1 · 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.

Original languageEnglish (US)
Pages (from-to)755-762
Number of pages8
JournalCanadian Journal of Physiology and Pharmacology
Volume77
Issue number10
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

Fingerprint

Bezafibrate
Fructose
Blood Vessels
Blood Pressure
Pharmaceutical Preparations
Lipids
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
VLDL Lipoproteins
Hypertension
Nonesterified Fatty Acids
Aorta
Triglycerides
Calcium Channel Agonists
Metabolic Syndrome X
Diet
Hypertriglyceridemia
Hyperinsulinism
Drinking Water

Keywords

  • Aortae
  • Free fatty acids
  • Hypertriglyceridemia
  • Sprague-Dawley rats
  • Vascular reactivity

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

Cite this

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abstract = "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 · kg-1 · 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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