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15-Hydroxyeicosatetraenoic acid and diabetic endothelial dysfunction in rabbit aorta
B Tesfamariam1, M L Brown, R A Cohen
1Robert Dawson Evans Department of Clinical Research, Boston University School of Medicine, MA 02118, USA.
Journal of Cardiovascular Pharmacology
|May 1, 1995
Summary
Diabetes increases 15-hydroxyeicosatetraenoic acid (HETE) release from aorta, impairing blood vessel function. This abnormal eicosanoid metabolism contributes to endothelial dysfunction and vasoconstriction in diabetic rabbits.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Metabolism
Background:
- Diabetes mellitus is associated with endothelial dysfunction.
- Eicosanoid metabolism plays a critical role in vascular tone regulation.
- Alloxan-induced diabetes in rabbits serves as a model for studying diabetic complications.
Purpose of the Study:
- To investigate the impact of diabetes on eicosanoid metabolism, specifically 15-hydroxyeicosatetraenoic acid (15-HETE).
- To determine the role of 15-HETE in endothelium-dependent relaxation and vasoconstriction in diabetic aorta.
- To elucidate the mechanism by which abnormal 15-HETE contributes to vascular dysfunction in diabetes.
Main Methods:
- Isolated aortic segments from alloxan-induced diabetic and normal rabbits were used.
- Aortic segments were incubated in high glucose concentrations to mimic diabetic conditions.
- Levels of immunoreactive 15-HETE were measured in incubation media.
- Vascular responses (contractions and relaxations) were assessed in aortic rings.
- Pharmacological agents, including cyclooxygenase inhibitors and prostaglandin receptor blockers, were employed.
Main Results:
- Diabetic rabbit aortas showed significantly greater basal and acetylcholine-stimulated release of 15-HETE compared to normal aortas.
- High glucose incubation of normal rabbit aortas increased 15-HETE release, particularly in segments with intact endothelium.
- 15-HETE induced aortic ring contractions, mediated via prostaglandin H2 (PGH2)/thromboxane A2 (TXA2) receptors.
- Subthreshold concentrations of 15-HETE impaired acetylcholine-induced relaxation, an effect blocked by a TXA2 receptor antagonist.
Conclusions:
- Abnormal, increased release of endothelium-derived 15-HETE occurs in diabetes.
- This elevated 15-HETE contributes to endothelial dysfunction and increased vasoconstriction in diabetes.
- The mechanism involves the interaction of 15-HETE with PGH2/TXA2 receptors, leading to impaired vascular relaxation and enhanced contraction.