Abstract 515: Serotonin Relaxes the Superior Mesenteric Vein: Implications for Blood Pressure Control
Serotonin (5-HT, 5-hydroxytryptamine) reduces blood pressure of the conscious rat when administered chronically (one week). 5-HT does not directly relax isolated arteries, and microsphere experiments in 5-HT-infused rats suggested that 5-HT increased flow to the splanchnic bed. We hypothesized that 5-HT increased splanchnic flow because of direct venous relaxation, and not indirect removal of arterial sympathetic tone. Surgical removal of sympathetic innervation of the splanchnic circulation did not alter the ability of 5-HT to lower blood pressure, allowing us to focus on the venous vasculature. Real time RT-PCR, immunohistochemistry and Western analyses supported the predominant expression of the 5-HT2B and 5-HT7 receptor in the superior mesenteric vein. The superior mesenteric vein was mounted in tissue baths for measurement of isometric contraction. 5-HT caused a concentration-dependent relaxation of the endothelin-1 (ET-1) contracted vein. The threshold of 5-HT-induced venous relaxation was significantly lower than for 5-HT-induced venous contraction (1 nM vs 1 μM, respectively). A series of serotonergic agonists was tested, and 5-carboxamidotryptamine (5-CT; mixed 5-HT1, 5-HT7 receptor agonist) and 5-HT were most potent in causing relaxation. Consistent with these findings, the 5-HT7 receptor antagonists, SB 266970 and LY215840, but not the 5-HT2B receptor antagonist LY272015 abolished 5-CT-induced relaxation of the isolated superior mesenteric vein (figure). These studies support the ability of 5-HT to directly relax veins, thereby increasing venous capacitance with a concomitant fall in blood pressure.
Author Disclosures: S.W. Watts: B. Research Grant (includes principal investigator, collaborator, or consultant and pending grants as well as grants already received); Significant; NIh HL107495. E. Darios: None. B.M. Seitz: None. R. Burnett: None. J.M. Thompson: None.
- © 2014 by American Heart Association, Inc.