Publication:
Improvement of vascular function by chronic administration of a cyclo-oxygenase inhibitor in cholesterol-fed rabbits

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Issued Date

2003

Resource Type

Article

File Type

application/pdf

ISSN

3051870

DOI

10.1046/j.1440-1681.2003.03850.x

Other identifier(s)

2-s2.0-0038809114

Rights Holder(s)

มหาวิทยาลัยศรีนครินทรวิโรฒ

Bibliographic Citation

Clinical and Experimental Pharmacology and Physiology. Vol 30, (2003), p.405-412

Suggested Citation

Srisawat S., Phivthong-Ngam L., Unchern S., Chantharaksri U., Govitrapong P., Sanvarinda Y. Improvement of vascular function by chronic administration of a cyclo-oxygenase inhibitor in cholesterol-fed rabbits. Clinical and Experimental Pharmacology and Physiology. Vol 30, (2003), p.405-412. doi:10.1046/j.1440-1681.2003.03850.x Retrieved from: https://hdl.handle.net/20.500.14740/6586

Title

Improvement of vascular function by chronic administration of a cyclo-oxygenase inhibitor in cholesterol-fed rabbits

Author(s)

Srisawat S.
 Phivthong-Ngam L.
 Unchern S.
 Chantharaksri U.
 Govitrapong P.
 Sanvarinda Y.

Abstract

1. Atherosclerotic cardio- and cerebrovascular disease is a leading cause of mortality in Western countries. Aspirin-like drugs are widely used to prevent and treat these occlusive cardio- and cerebrovascular diseases. The beneficial effects of these drugs have been largely attributed to inhibition of platelet cyclo-oxygenase activity and thromboxane (TX) A2 production. We investigated the effect of an aspirin-like drug, namely indomethacin, on endothelial function, plaque and platelet aggregation and the formation of vasoactive substances during the development of atherosclerosis in cholesterol-fed rabbits. 2. Rabbits were fed 1% cholesterol (n = 8), 1% cholesterol plus 25 mg/day indomethacin (n = 8) or normal rabbit chow (control group; n = 8) for 12 weeks. Urinary excretion rates of 2,3-dinor-TXB2, 6-keto-prostaglandin (PG) F1α, 8-iso-PGF2α, and nitrate were analysed at the beginning of dietary intervention and at 4 weekly intervals thereafter. At the end of the study period, platelet aggregation, aortic plaque formation and endothelium-dependent and -independent vascular functions of isolated aortic rings ex vivo were assessed. 3. Compared with control, in the cholesterol-fed group, urinary 2,3-dinor-TXB2, 6-keto-PGF1α and 8-iso-PGF2α excretion and platelet aggregation were significantly increased (P < 0.05), but urinary excretion of nitrate was decreased (P < 0.05). Treatment with indomethacin significantly reduced platelet aggregation, urinary 2,3-dinor-TXB2, 6-keto-PGF1α, and 8-iso-PGF2α excretion (P < 0.05 vs the cholesterol-fed group) and attenuated the reduction in urinary nitrate excretion. 4. Cholesterol feeding progressively increased aortic intimal thickening and impaired endothelium-dependent vasodilator function (P < 0.05 vs control), whereas indomethacin partially prevented aortic plaque formation and restored endothelium-dependent vasodilation (P < 0.05 vs the cholesterol-fed group). 5. The present study demonstrates that indomethacin reduces the progression of atherosclerotic lesions and improves endothelium-mediated vascular responses ex vivo in cholesterol-fed rabbits. The beneficial effects of indomethacin may be due to its ability to prevent the elevation of platelet aggregation, TXA2 (measured as urinary 2,3-dinor-TXB2 excretion) and 8-iso-PGF2α, formation and to retard the decrease in endogenous nitric oxide synthesis (assessed as urinary excretion of nitrate). Despite indomethacin treatment leading to the suppression of prostacyclin biosynthesis (assessed as urinary 6-keto-PGF1α excretion), according to our data, indomethacin appears to preserve endothelial function.

Subject(s)

2,3 dinorthromboxane B2
 6 oxoprostaglandin F1 alpha
 8 isoprostaglandin F2 alpha
 Acetylsalicylic acid
 Cholesterol
 Indometacin
 Nitrate
 Nitric oxide
 Prostacyclin
 Prostaglandin synthase inhibitor
 Thromboxane A2
 Animal cell
 Animal model
 Animal tissue
 Artery intima proliferation
 Article
 Atherosclerosis
 Atherosclerotic plaque
 Blood vessel function
 Cerebrovascular disease
 Controlled study
 Coronary artery atherosclerosis
 Diet
 Endothelium
 Male
 Mortality
 Nonhuman
 Rabbit
 Thrombocyte aggregation
 Urinary excretion
 Animals
 Aorta, Thoracic
 Arteriosclerosis
 Cholesterol, Dietary
 Cyclooxygenase Inhibitors
 Endothelium, Vascular
 Male
 Rabbits
 Vasodilation

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URI

https://hdl.handle.net/20.500.14740/6586

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Scopus: Year 1983-2021

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