Equine coronary artery responds to 5-hydroxytryptamine with relaxation in vitro.
Abstract: Isolated equine coronary arteries responded to 5-hydroxytryptamine (5-HT) with relaxations in both endothelium-dependent and endothelium-independent mechanisms. Experiments were designed to characterize the 5-HT receptor subtype mediating these relaxations. Both 5-HT and alpha-methyl-5-HT (alpha-Me-5-HT; 5-HT2 agonist) produced concentration-dependent relaxations in equine coronary arteries precontracted with a thromboxane A2 derivative (ONO11113). The degree of the maximal relaxation induced by alpha-Me-5-HT was about one-half of that induced by 5-HT. In the coronary arteries without endothelium, alpha-Me-5-HT produced no relaxation, but 5-HT caused relaxation, which was inhibited by a 5-HT1 antagonist (methysergide, mianserin and methiothepin), but was inhibited neither by ketanserin (5-HT2 antagonist) nor by MDL72222 (5-HT3 antagonist). In the coronary arteries with endothelium, however, the relaxation induced by alpha-Me-5-HT was inhibited by ketanserin, L-nitro-arginine (NO synthase inhibitor) and methylene blue (soluble guanylate cyclase inhibitor). These results suggest that the relaxation induced by 5-HT in equine coronary arteries depends mainly on the stimulation of both 5-HT1 receptor subtype on smooth muscle cells directly, and 5-HT2 receptor subtype on endothelial cells indirectly by liberating endothelium-derived NO.
Publication Date: 1994-06-01 PubMed ID: 7933060DOI: 10.1111/j.1365-2885.1994.tb00236.xGoogle Scholar: Lookup
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Summary
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This study investigates how isolated horse coronary arteries react to 5-hydroxytryptamine (5-HT), suggesting that their relaxation is largely due to the stimulation of both the 5-HT1 receptor subtype on smooth muscle cells and the 5-HT2 receptor subtype on endothelial cells.
Methodology and Findings
- The researchers designed experiments to explore the subtype of receptor within the 5-HT mechanism responsible for these relaxations, working with equine coronary arteries in a controlled laboratory setting.
- They pre-compressed these arteries using ONO11113, a thromboxane A2 derivative, then introduced concentrations of either 5-HT or alpha-methyl-5-HT, which is a 5-HT2 agonist.
- The study found that both substances caused the arteries to relax. However, the relaxation ability of alpha-Me-5-HT was about half of that of 5-HT.
- In arteries without endothelium, alpha-Me-5-HT had no effect, but 5-HT did cause relaxation. This relaxation was blocked by 5-HT1 antagonists (methysergide, mianserin, and methiothepin), but was not affected by either a 5-HT2 antagonist (ketanserin) or a 5-HT3 antagonist (MDL72222).
Significance of Results
- In arteries that did have an endothelium layer, the relaxation achieved by alpha-Me-5-HT was impeded by ketanserin, L-nitro-arginine (an inhibitor of nitric oxide synthase), and methylene blue (which impedes soluble guanylate cyclase).
- This suggests that the primary role of 5-HT in relaxing equine coronary arteries is stimulating the 5-HT1 receptor subtype directly on smooth muscle cells, and the 5-HT2 receptor subtype on endothelial cells indirectly, by releasing endothelium-derived nitric oxide (NO).
- This implies that 5-HT, or substances acting on the 5-HT receptors, could potentially be used for therapeutic interventions to treat equines with coronary artery diseases.
- This research may also provide further insights into human coronary function as many aspects of cardiovascular physiology and pharmacology are similar in humans and equines.
Cite This Article
APA
Obi T, Kabeyama A, Nishio A.
(1994).
Equine coronary artery responds to 5-hydroxytryptamine with relaxation in vitro.
J Vet Pharmacol Ther, 17(3), 218-225.
https://doi.org/10.1111/j.1365-2885.1994.tb00236.x Publication
Researcher Affiliations
- Department of Veterinary Pharmacology, Faculty of Agriculture, Kagoshima University, Japan.
MeSH Terms
- Animals
- Arteries
- Coronary Vessels / drug effects
- Electrophysiology
- Endothelium, Vascular / metabolism
- Horses
- In Vitro Techniques
- Muscle Relaxation / drug effects
- Muscle, Smooth, Vascular / drug effects
- Receptors, Serotonin / metabolism
- Serotonin / analogs & derivatives
- Serotonin / pharmacology
- Serotonin Antagonists / pharmacology
Citations
This article has been cited 4 times.- Watts SW, Morrison SF, Davis RP, Barman SM. Serotonin and blood pressure regulation. Pharmacol Rev 2012 Apr;64(2):359-88.
- Villalón CM, Centurión D. Cardiovascular responses produced by 5-hydroxytriptamine:a pharmacological update on the receptors/mechanisms involved and therapeutic implications. Naunyn Schmiedebergs Arch Pharmacol 2007 Oct;376(1-2):45-63.
- Miyamoto A, Obi T, Nishio A. The vasomotor effects of 5-hydroxytryptamine on equine basilar arteries in vitro. Vet Res Commun 1996;20(1):61-70.
- Ootawa T, Wu S, Sekio R, Smith H, Islam MZ, Nguyen HTT, Uno Y, Shiraishi M, Miyamoto A. Characterization of Vasoreactivity in a Semi-Arboreal Snake, the Tokara Habu (Protobothrops tokarensis). Animals (Basel) 2023 Nov 23;13(23).
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