Abstract
We analyzed the modulation of serotonin on the bradycardia induced in vivo by vagal electrical stimulation in alloxan-induced long-term diabetic rats. Bolus intravenous administration of serotonin had a dual effect on the bradycardia induced either by vagal stimulation or exogenous Ach, increasing it at low doses and decreasing it at high doses of 5-hydroxytryptamine (5-HT), effect reproduced by 5-carboxamidotryptamine maleate (5-CT), a 5-HT1/7 agonist. The enhancement of the bradycardia at low doses of 5-CT was reproduced by 5-HT1A agonist 8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT) and abolished by WAY-100,635, 5-HT1A antagonist. Pretreatment with 5-HT1 antagonist methiothepin blocked the stimulatory and inhibitory effect of 5-CT, whereas pimozide, 5-HT7 antagonist, only abolished 5-CT inhibitory action. In conclusion, long-term diabetes elicits changes in the subtype of the 5-HT receptor involved in modulation of vagally induced bradycardia. Activation of the 5-HT1A receptors induces enhancement, whereas attenuation is due to 5-HT7 receptor activation. This 5-HT dual effect occurs at pre- and postjunctional levels.
Highlights
The role of 5-hydroxytryptamine (5-HT) in cholinergic neurotransmission and parasympathetic cardiovascular effects has received considerable attention over many years
This was achieved by examining the serotonergic receptors involved in the cholinergic cardiac responses induced by vagal electrical stimulation or by the administration of exogenous acetylcholine during experimental alloxaninduced diabetes
Alloxan is a diabetogenic agent which induces a syndrome in animals resembling type 1 diabetes mellitus characterized by hyperglycemia, hypercholesterolemia, glycosuria, and raised levels of glycosylated hemoglobin in erythrocytes [12, 17, 21,22,23,24]
Summary
The role of 5-hydroxytryptamine (5-HT) in cholinergic neurotransmission and parasympathetic cardiovascular effects has received considerable attention over many years. Central 5-HT1A, 5-HT3, and 5-HT7 receptors have a physiological role in the regulation of cardiovascular reflexes, controlling changes in parasympathetic (vagal) drive to the heart [1]. Other reports have suggested an inhibitory serotonergic effect on acetylcholine (Ach) release via activation of 5-HT1 receptors [10]. In pithed rats, the serotonergic mechanisms involved in cardiac cholinergic neurotransmission are presynaptic and that they can dually inhibit or facilitate acetylcholine release via activation of 5-HT2 or 5HT3 receptors, respectively [11]. We have shown that experimental diabetes elicits changes in the nature and 5HT receptor type/subtype involved in vagal bradycardia stimulated by electrical means [12]
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