15-Lipoxygenase metabolites contribute to age-related reduction in acetylcholine-induced hypotension in rabbits
- 1 July 2008
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 295 (1), H89-H96
- https://doi.org/10.1152/ajpheart.00054.2008
Abstract
Arachidonic acid (AA) metabolites from the 15-lipoxygenase-1 (15-LO-1) pathway, trihydroxyeicosatrienoic acids (THETAs) and hydroxy-epoxyeicosatrienoic acids (HEETAs), are endothelium-derived hyperpolarizing factors (EDHFs) and relax rabbit arteries. Rabbit vascular 15-LO-1 expression, THETA and HEETA synthesis, and nitric oxide and prostaglandin-independent relaxations to acetylcholine (ACh) and AA decreased with age (neonates to 16-wk-old). We characterized age-dependent ACh-hypotensive responses in vivo in 1-, 4-, 8-, and 16-wk-old rabbits and the contribution of THETAs and HEETAs to these responses. In anesthetized rabbits, blood pressure responses to ACh (4–4,000 ng/kg) were determined in the presence of vehicle or various inhibitors. ACh responses decreased with age ( P > 0.001). In the absence or presence of Nω-nitro-l-arginine methyl ester (l-NAME) and indomethacin (Indo), maximum responses in 1 (−54.7 ± 7.4 and −37.9 ± 3.9%)- and 4 (−48.8 ± 2.4 and −35.5 ± 7.8%)-wk-old rabbits were higher than 8 (−30.0 ± 2.8 and −26.6 ± 4.4%)- and 16 (−36.7 ± 3.5 and −27.3 ± 10%)-wk-old rabbits. A lipoxygenase inhibitor, BW755C, reduced THETA and HEETA synthesis in mesenteric arteries. In the presence of Indo and Nω-nitro-l-arginine, ACh relaxations were reduced by BW755C to a greater extent in the mesenteric arteries from the younger rabbits. In 4-wk-old rabbits treated with l-NAME and Indo, the maximum ACh hypotension was reduced by the potassium channel inhibitors apamin and charybdotoxin to −6.9 ± 0.9%, by apamin alone to −19.5 ± 1.4%, and by BW755C to −18.8 ± 3.5%. The present study indicates that the age-related decrease in ACh-induced hypotension is mediated by the decreased synthesis of the 15-LO-1 metabolites THETAs and HEETAs.Keywords
This publication has 37 references indexed in Scilit:
- Age-related decrease in 15-lipoxygenase contributes to reduced vasorelaxation in rabbit aortaAmerican Journal of Physiology-Heart and Circulatory Physiology, 2008
- Endothelial 15-Lipoxygenase-1 Overexpression Increases Acetylcholine-Induced Hypotension and Vasorelaxation in RabbitsHypertension, 2008
- S-acylation regulates Kv1.5 channel surface expressionAmerican Journal of Physiology-Cell Physiology, 2007
- ACh-induced relaxations of rabbit small mesenteric arteries: role of arachidonic acid metabolites and K+American Journal of Physiology-Heart and Circulatory Physiology, 2007
- Adenoviral expression of 15-lipoxygenase-1 in rabbit aortic endothelium: role in arachidonic acid-induced relaxationAmerican Journal of Physiology-Heart and Circulatory Physiology, 2007
- Endothelium-Derived Hyperpolarizing FactorArteriosclerosis, Thrombosis, and Vascular Biology, 2006
- Reticulocyte 15-Lipoxygenase-I Is Important in Acetylcholine-Induced Endothelium-Dependent Vasorelaxation in Rabbit AortaArteriosclerosis, Thrombosis, and Vascular Biology, 2006
- Apamin-Sensitive K + Currents Mediate Arachidonic Acid-Induced Relaxations of Rabbit AortaHypertension, 2004
- 5,6-Epoxyeicosatrienoic Acid Mediates the Enhanced Renal Vasodilation to Arachidonic Acid in the SHRHypertension, 2003
- Chronic Hypoxia Activates Lung 15-Lipoxygenase, Which Catalyzes Production of 15-HETE and Enhances Constriction in Neonatal Rabbit Pulmonary ArteriesCirculation Research, 2003