Role of peripheral 5-HT receptors in 5-HT-induced cardiac sympatho-inhibition in type 1 diabetic rats.

5-HT inhibits cardiac sympathetic neurotransmission in normoglycaemic rats, via 5-HT, 5-HT and 5-HT receptor activation. Since type 1 diabetes impairs the cardiac sympathetic innervation leading to cardiopathies, this study aimed to investigate whether the serotonergic influence on cardiac noradrenergic control is altered in type 1 diabetic rats. Diabetes was induced in male Wistar rats by streptozotocin (50 mg/kg, i.p.). Four weeks later, the rats were anaesthetized, pithed and prepared for producing tachycardic responses by electrical preganglionic stimulation (C-T) of the cardioaccelerator sympathetic outflow or i.v. noradrenaline bolus injections. Immunohistochemistry was performed to study 5-HT, 5-HT and 5-HT receptor expression in the stellate ganglion from normoglycaemic and diabetic rats. In the diabetic group, i) i.v. continuous infusions of 5-HT induced a cardiac sympatho-inhibition that was mimicked by the 5-HT agonist 5-carboxamidotryptamine (without modifying noradrenaline-induced tachycardia), but not by the agonists indorenate (5-HT), CP 93,129 (5-HT), PNU 142633 (5-HT), or LY344864 (5-HT); ii) SB 699551 (5-HT antagonist; i.v.) completely reversed 5-CT-induced cardiac sympatho-inhibition; and iii) 5-HT receptors were more expressed in the stellate ganglion compared to normoglycaemic rats. These results show the prominent role of the peripheral 5-HT receptors prejunctionally inhibiting the cardiac sympathetic drive in type 1 diabetic rats.