5-HT is a potent relaxant in rat superior mesenteric veins

Serotonin (5-HT, 5-hydroxytryptamine) reduces blood pressure of the conscious 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-HT(2B) and 5-HT(7) 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 endothelin-1 (ET-1)-contracted vein. The threshold of 5-HT-induced venous relaxation 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 order of potency found for agonist-induced relaxation (receptor selectivity): 5-CT (5-HT(1)/5-HT(7))>5-HT = LP-44 (5-HT(7))>PNU109291 (5-HT(1D)) = BW723C86 (5-HT(2B)). 8-OH-DPAT (5-HT(1A/7)), CP93129 (5-HT(1B)), mCPBG (5-HT(3/4)), AS19 (5-HT(7)) and TCB-2 (5-HT(2A)) did not relax the isolated vein. Consistent with these findings, two different 5-HT(7) receptor antagonists SB 269970 and LY215840 but not the 5-HT(2B) receptor antagonist LY272015 nor the nitric oxide synthase inhibitor LNNA abolished 5-CT-induced relaxation of the isolated SMV. 5-CT (1 μg kg(−1) min(−1), sc) also reduced blood pressure over 7 days. These findings suggest that 5-HT directly relaxes the SMV primarily through activation of the 5-HT(7) receptor.