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DIABETES‐INDUCED CHANGES IN 5‐HYDROXYTRYPTAMINE MODULATION OF VAGALLY INDUCED BRADYCARDIA IN RAT HEART
Author(s) -
García Mónica,
Morán Asunción,
Martín M Luisa,
Ortizde Urbina A Vega,
San Román Luis
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04688.x
Subject(s) - bradycardia , endocrinology , medicine , agonist , stimulation , vagus nerve , chemistry , heart rate , receptor , blood pressure
SUMMARY1 In the present study, we investigated how alloxan‐induced diabetes affects the ability of 5‐hydroxytryptamine (5‐HT) to modulate bradycardia induced in vivo by electrical stimulation of the vagus nerve in pithed rats. We also analysed the type and/or subtype of 5‐HT receptors involved. 2 Diabetes was induced in male Wistar rats with a single injection of alloxan (150 mg/kg, s.c.). Four weeks later, rats were anaesthetized, pretreated with atenolol and pithed. Electrical stimulation (3, 6 and 9 Hz) of the vagus nerve resulted in frequency dependent decreases in heart rate (HR). 3 In diabetic rats, intravenous bolus administration of high doses of 5‐HT (100 and 200 µg/kg) increased the bradycardia induced by vagal electrical stimulation. Similarly, low doses (10 µg/kg) of the 5‐HT 1/7 receptor agonist 5‐carboxamidotryptamine (5‐CT), increased vagally induced bradycardia. However, at high doses (50, 100 and 150 µg/kg), 5‐CT reduced the bradycardia. Attenuation of the vagally induced bradycardia evoked by the higher doses of 5‐CT was reproduced by L‐694,247 (50 µg/kg), a selective agonist for the non‐rodent 5‐HT 1B and 5‐HT 1D receptors. Enhancement of the vagally induced bradycardia elicited by low doses of 5‐CT was reproduced by the selective 5‐HT 1A receptor agonist 8‐hydroxydipropylaminotretalin hydrobromide (8‐OH‐DPAT; 50 µg/kg). These stimulatory and inhibitory actions on vagal stimulation‐induced bradycardia in diabetic rats were also observed after administration of exogenous acetylcholine. 4 Vagally induced bradycardia in diabetic rats was not affected by administration of the selective 5‐HT 2 receptor agonist α‐methyl‐5‐HT (150 µg/kg), the selective 5‐HT 3 receptor agonist 1‐phenylbiguanide (150 µg/kg) or the selective 5‐HT 1B receptor agonist CGS‐12066B (50 µg/kg). 5 Enhancement of the electrical stimulation‐induced bradycardia in diabetic rats caused by 5‐CT (10 µg/kg) or 8‐OH‐DPAT (50 µg/kg) was abolished by the selective 5‐HT 2/7 receptor antagonist mesulergine (1 mg/kg) and the selective 5‐HT 1A receptor antagonist WAY‐100,635 (100 µg/kg), respectively. Similarly, pretreatment with the non‐selective 5‐HT 1 receptor antagonist methiothepin (0.1 mg/kg) blocked the inhibitory effect of 5‐CT (50 µg/kg) on the bradycardia induced by vagal electrical stimulation in diabetic rats. BRL‐15572 (2 µg/kg), a selective 5‐HT 1D receptor antagonist, inhibited the action of L‐694,247 (50 µg/kg), a selective agonist for the non‐rodent 5‐HT 1B and 5‐HT 1D receptors, on the vagally induced bradycardia. 6 In conclusion, in the present study, experimental diabetes evoked changes in both the nature and 5‐HT receptor types/subtypes involved in vagally induced bradycardia.