Funding Information This work is supported by the National Institutes of Health HL107495.

Serotonin (5-HT, 5-hydroxytryptamine) reduces blood pressure of the con-scious rat when administered chronically (1 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; our focus was thus on the superior mesenteric vein (SMV) as an important vein in splanchnic circulation. Real-time RT-PCR, immunohistochemistry and Western analyses supported the predominant expression of the 5-HT2B and 5-HT7 receptor in the SMV. The SMV was mounted in tissue baths for measurement of isometric contraction. 5-HT caused a concentration-dependent relaxation of the endo-thelin-1 (ET-1)-contracted vein. The threshold of 5-HT-induced venous relaxa-tion was significantly lower than for 5-HT-induced venous contraction (~2 vs. 700 nmol/L, respectively). A series of serotonergic agonists established in their use of receptor characterization was tested, and the following rank orde