Role of peripheral 5-HT(5A) 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(1B), 5-HT(1D) and 5-HT(5A) 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(7)-T(1)) of the cardioaccelerator sympathetic outflow or i.v. noradrenaline bolus injections. Immunohistochemistry was performed to study 5-HT(1B), 5-HT(1D) and 5-HT(5A) 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(1/5A) agonist 5-carboxamidotryptamine (without modifying noradrenaline-induced tachycardia), but not by the agonists indorenate (5-HT(1A)), CP 93,129 (5-HT(1B)), PNU 142633 (5-HT(1D)), or LY344864 (5-HT(1F)); ii) SB 699551 (5-HT(5A) antagonist; i.v.) completely reversed 5-CT-induced cardiac sympatho-inhibition; and iii) 5-HT(5A) receptors were more expressed in the stellate ganglion compared to normoglycaemic rats. These results show the prominent role of the peripheral 5-HT(5A) receptors prejunctionally inhibiting the cardiac sympathetic drive in type 1 diabetic rats.