5-Hydroxytryptamine does not reduce sympathetic nerve activity or neuroeffector function in the splanchnic circulation

• Published in: European journal of pharmacology 2015-05, Vol.754, p.140-147
• Main Authors: Darios, Emma S., Barman, Susan M., Orer, Hakan S., Morrison, Shaun F., Davis, Robert P., Seitz, Bridget M., Burnett, Robert, Watts, Stephanie W.
• Format: Article
• Language: English
• Subjects: 5-HT; Animals; Blood pressure; Blood Pressure - drug effects; Blood Pressure - physiology; Dose-Response Relationship, Drug; Electric Stimulation; Ganglia, Sympathetic - surgery; Male; Mesenteric Artery, Superior - drug effects; Mesenteric Artery, Superior - physiology; Pyridines - pharmacology; Pyrroles - pharmacology; Rats; Serotonin - analogs & derivatives; Serotonin - pharmacology; Serotonin - physiology; Serotonin Receptor Agonists - pharmacology; Splanchnic Circulation - drug effects; Splanchnic Circulation - physiology; Splanchnic Nerves - drug effects; Splanchnic Nerves - physiology; Sympathetic nerve activity; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiology; Vasoconstriction - drug effects; Vasoconstriction - physiology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2015.02.032

Infusion of 5-hydroxytryptamine (5-HT) in conscious rats results in a sustained (up to 30 days) fall in blood pressure. This is accompanied by an increase in splanchnic blood flow. Because the splanchnic circulation is regulated by the sympathetic nervous system, we hypothesized that 5-HT would: 1) directly reduce sympathetic nerve activity in the splanchnic region; and/or 2) inhibit sympathetic neuroeffector function in splanchnic blood vessels. Moreover, removal of the sympathetic innervation of the splanchnic circulation (celiac ganglionectomy) would reduce 5-HT-induced hypotension. In anaesthetized Sprague-Dawley rats, mean blood pressure was reduced from 101±4 to 63±3mm Hg during slow infusion of 5-HT (25μg/kg/min, i.v.). Pre- and postganglionic splanchnic sympathetic nerve activity were unaffected during 5-HT infusion. In superior mesenteric arterial rings prepared for electrical field stimulation, neither 5-HT (3, 10, 30nM), the 5-HT1B receptor agonist CP 93129 nor 5-HT1/7 receptor agonist 5-carboxamidotryptamine inhibited neurogenic contraction compared to vehicle. 5-HT did not inhibit neurogenic contraction in superior mesenteric venous rings. Finally, celiac ganglionectomy did not modify the magnitude of fall or time course of 5-HT-induced hypotension when compared to animals receiving sham ganglionectomy. We conclude it is unlikely 5-HT interacts with the sympathetic nervous system at the level of the splanchnic preganglionic or postganglionic nerve, as well as at the neuroeffector junction, to reduce blood pressure. These important studies allow us to rule out a direct interaction of 5-HT with the splanchnic sympathetic nervous system as a cause of the 5-HT-induced fall in blood pressure.