Diabetes‐induced changes in the 5‐hydroxytryptamine inhibitory receptors involved in the pressor effect elicited by sympathetic stimulation in the pithed rat

• Published in: British journal of pharmacology 2005-07, Vol.145 (5), p.593-601
• Main Authors: García, Mónica, Morán, Asunción, Calama, Elena, Martín, Maria Luisa, Barthelmebs, Mariette, Román, Luis San
• Format: Article
• Language: English
• Subjects: 5‐CT; 5‐HT1A receptors; 5‐Hydroxytryptamine; Animals; Atropine - pharmacology; Biological and medical sciences; Blood Glucose - metabolism; Blood Pressure - drug effects; Blood Pressure - physiology; Body Weight - drug effects; Decerebrate State - physiopathology; Diabetes Mellitus, Experimental - metabolism; Dose-Response Relationship, Drug; experimental diabetes; Hemodynamics - drug effects; Male; Medical sciences; Parasympatholytics - pharmacology; Pharmacology. Drug treatments; prejunctional inhibition; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT1A - drug effects; Receptors, Serotonin - drug effects; Receptors, Serotonin - physiology; Receptors, Serotonin, 5-HT1 - drug effects; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology; Stimulation, Chemical; Sympathetic Nervous System - physiology
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0706216

1 We investigated the effect of alloxan‐induced diabetes on the inhibitory mechanisms of 5‐hydroxytryptamine (5‐HT) in the pressor responses induced by stimulation of sympathetic vasopressor outflow in pithed rats, and analysed the type and/or subtype of 5‐HT receptors involved. 2 Diabetes was induced in male Wistar rats by a single s.c. injection of alloxan, then 4 weeks later, they were anaesthetized, pretreated with atropine and pithed. Electrical stimulation of the sympathetic outflow from the spinal cord (0.1, 0.5, 1 and 5 Hz) resulted in frequency‐dependent increases in blood pressure. 3 Intravenous infusions of 5‐HT (1–80 μg kg−1 min−1) reduced the pressor effects obtained by electrical stimulation. The 5‐HT1 receptor agonist 5‐carboxamidotryptamine, 5‐CT (5 μg kg−1 min−1), caused an inhibition of the pressor response, whereas the selective 5‐HT2 receptor agonist, α‐methyl‐5‐HT (5 μg kg−1 min−1) and the selective 5‐HT3 receptor agonist, 1‐phenylbiguanide (40 μg kg−1 min−1), did not modify the sympathetic pressor responses. 5‐HT had no effect on exogenous noradrenaline (NA)‐induced pressor responses. 4 The inhibition of electrically induced pressor responses by 5‐HT (10 μg kg−1 min−1) was unable to be elicited after i.v. treatment with methiothepin (100 μg kg−1) because of the marked inhibition produced by methiothepin alone. The 5‐HT‐induced inhibition was blocked after i.v. administration of WAY‐100,635 (100 μg kg−1) and not affected by ritanserin (1 mg kg−1), MDL 72222 (2 mg kg−1). 5 The selective 5‐HT1A receptor agonist, 8‐hydroxydipropylaminotretalin hydrobromide (8‐OH‐DPAT) (5–20 μg kg−1 min−1) but neither the rodent 5‐HT1B receptor agonist, CGS‐12066B (5 μg kg−1 min−1), nor the selective nonrodent 5‐HT1B and 5‐HT1D receptor agonist, L‐694,247 (5 and 40 μg kg−1 min−1), inhibited the electrically induced pressor response. The selective 5‐HT1A receptor antagonist, WAY‐100,635 (100 μg kg−1), blocked the inhibition induced by 8‐OH‐DPAT (10 μg kg−1 min−1). 8‐OH‐DPAT had no effect on exogenous NA‐induced pressor responses. 6 Experimental diabetes produces changes in the inhibitory effect induced by 5‐HT on electrically induced sympathetic pressor responses, such that the inhibitory action induced by 5‐HT in diabetic pithed rats is mediated by prejunctional 5‐HT1A receptors. British Journal of Pharmacology (2005) 145, 593–601. doi:10.1038/sj.bjp.0706216