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 language | English |
|---|---|
| Pages (from-to) | 1257-1262 |
| Number of pages | 6 |
| Journal | American Journal of Hypertension |
| Volume | 10 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 1997 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Effect of doxazosin on endothelial dysfunction in hypercholesterolemic/antioxidant-deficient rats
AU - Raij, Leopoldo
AU - Hayakawa, Hiroshi
AU - Coffee, Karen
AU - Guerra, Janeth
PY - 1997/11/1
Y1 - 1997/11/1
N2 - 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.
AB - 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.
KW - Antioxidants
KW - Doxazosin
KW - Endothelium
KW - Hypercholesterolemia
KW - Nitric oxide
KW - Vasorelaxation
UR - http://www.scopus.com/inward/record.url?scp=0031279383&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031279383&partnerID=8YFLogxK
U2 - 10.1016/S0895-7061(97)00265-3
DO - 10.1016/S0895-7061(97)00265-3
M3 - Article
C2 - 9397245
AN - SCOPUS:0031279383
VL - 10
SP - 1257
EP - 1262
JO - Journal of clinical hypertension
JF - Journal of clinical hypertension
SN - 0895-7061
IS - 11
ER -