Effect of doxazosin on endothelial dysfunction in hypercholesterolemic/antioxidant-deficient rats

Leopoldo Raij, Hiroshi Hayakawa, Karen Coffee, Janeth Guerra

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Hypertension, hypercholesterolemia, atherosclerosis, and coronary heart disease are associated with abnormal endothelium-dependent, nitric oxide- mediated vasorelaxation. In rats, hypercholesterolemia in combination with deficiencies of vitamin E and selenium results in increased endogenous lipid oxidation and endothelial dysfunction. Two hydroxymetabolites of doxazosin, an α1-adrenergic blocking antihypertensive agent, inhibit human lipid oxidation in vitro in a dose-dependent fashion. The present studies were performed to determine the effect of in vivo treatment with doxazosin on endothelial dysfunction in hypercholesterolemic/antioxidant-deficient rats. Dahl rats were fed 1) a standard diet, 2) a high cholesterol (4%) diet, or 3) a high cholesterol, vitamin E- and selenium-deficient diet. A subgroup of animals in each group were administered doxazosin (3.5 mg/100 g/day) for 16 weeks. In the aortas, vascular relaxations induced by acetylcholine were significantly decreased (P < .05) in high cholesterol/antioxidant-deficient rats compared with normal and high cholesterol animals. Doxazosin treatment prevented the impairment in endothelium-dependent vascular relaxation in the high cholesterol/antioxidant-deficient group. Vasorelaxation in response to the exogenous nitric oxide donor diethylamine nanoate, which was significantly impaired (P < .05) in aortas from high cholesterol/antioxidant- deficient animals compared with normal and high cholesterol animals, was normalized in aortas from high cholesterol/antioxidant-deficient animals that had received doxazosin. The antioxidant effect of doxazosin may have therapeutic implications in diseases associated with endothelial dysfunction linked to products of lipid oxidation.

Original languageEnglish
Pages (from-to)1257-1262
Number of pages6
JournalAmerican Journal of Hypertension
Volume10
Issue number11
DOIs
StatePublished - Nov 1 1997
Externally publishedYes

Fingerprint

Doxazosin
Antioxidants
Cholesterol
Vasodilation
Aorta
Selenium
Diet
Hypercholesterolemia
Lipids
Inbred Dahl Rats
Vitamin E Deficiency
Adrenergic Antagonists
Nitric Oxide Donors
Vitamin E
Antihypertensive Agents
Acetylcholine
Endothelium
Coronary Disease
Blood Vessels
Atherosclerosis

Keywords

  • Antioxidants
  • Doxazosin
  • Endothelium
  • Hypercholesterolemia
  • Nitric oxide
  • Vasorelaxation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Effect of doxazosin on endothelial dysfunction in hypercholesterolemic/antioxidant-deficient rats. / Raij, Leopoldo; Hayakawa, Hiroshi; Coffee, Karen; Guerra, Janeth.

In: American Journal of Hypertension, Vol. 10, No. 11, 01.11.1997, p. 1257-1262.

Research output: Contribution to journalArticle

Raij, Leopoldo ; Hayakawa, Hiroshi ; Coffee, Karen ; Guerra, Janeth. / Effect of doxazosin on endothelial dysfunction in hypercholesterolemic/antioxidant-deficient rats. In: American Journal of Hypertension. 1997 ; Vol. 10, No. 11. pp. 1257-1262.
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