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Mesenteric vasodilator effect of 5-hydroxytryptamine: possible enteric neuron mediation
Archives Internationales De Pharmacodynamie Et De Therapie
|June 1, 1976
Summary
Serotonin (5-HT) causes vasodilation in cats when intestinal nerves are cut, but higher doses cause constriction with intact nerves. This suggests nerve activity significantly modulates serotonin's vascular effects.
Area of Science:
- Physiology
- Pharmacology
- Vascular Biology
Background:
- Serotonin (5-hydroxytryptamine, 5-HT) is a key neurotransmitter and hormone.
- Its role in regulating mesenteric blood flow is complex and potentially dose-dependent.
- Nervous system modulation of vascular responses to vasoactive substances requires further elucidation.
Purpose of the Study:
- To investigate the effect of serotonin (5-HT) on superior mesenteric blood flow in anesthetized cats.
- To determine the influence of intestinal nerve activity on the vascular response to 5-HT.
- To characterize the mechanisms underlying 5-HT-induced changes in mesenteric circulation.
Main Methods:
- Intra-arterial injections and infusions of 5-HT were administered to anesthetized cats.
- Superior mesenteric periarterial nerves were manipulated surgically (sectioning) and pharmacologically.
- Vascular responses were assessed under conditions of intact and altered nerve activity, including alpha-adrenergic blockade.
- Responses were differentiated from systemic arterial pressure or intestinal motility changes.
Main Results:
- Low doses of 5-HT (<5 mug) caused vasodilation with intact nerves, while higher doses caused vasoconstriction.
- Sectioning periarterial nerves resulted in vasodilation across the entire dose range of 5-HT.
- Doses of 5-HT initially causing vasoconstriction elicited vasodilation after nerve sectioning and alpha-adrenergic blockade.
- The vasodilator response was resistant to adrenergic, cholinergic, and histaminergic blockade but sensitive to tetrodotoxin and dihydroergotamine.
Conclusions:
- Superior mesenteric vascular responses to 5-HT are significantly modulated by the periarterial nerve supply.
- Nerve sectioning unmasks or enhances a dose-dependent vasodilator response to 5-HT.
- The vasodilator effect appears to be mediated by a tetrodotoxin-sensitive mechanism, possibly involving non-adrenergic, non-cholinergic pathways, and is antagonized by dihydroergotamine.