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- Title
5-HT is a potent relaxant in rat superior mesenteric veins.
- Authors
Watts, Stephanie W.; Darios, Emma S.; Seitz, Bridget M.; Thompson, Janice M.
- Abstract
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- 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 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-HT1/5-HT7)>5-HT = LP-44 (5-HT7)>PNU109291 (5-HT1D) = BW723C86 (5-HT2B). 8-OH-DPAT (5-HT1A/7), CP93129 (5-HT1B), mCPBG (5-HT3/4), AS19 (5-HT7) and TCB-2 (5-HT2A) did not relax the isolated vein. Consistent with these findings, two different 5-HT7 receptor antagonists SB 269970 and LY215840 but not the 5-HT2B 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- HT7 receptor.
- Subjects
SEROTONIN; REGULATION of blood pressure; LABORATORY rats; SPLANCHNIC nerves; IMMUNOHISTOCHEMISTRY; MESENTERIC veins; THERAPEUTICS
- Publication
Pharmacology Research & Perspectives, 2015, Vol 3, Issue 1, pn/a
- ISSN
2052-1707
- Publication type
Article
- DOI
10.1002/prp2.103