Long-term serotonin administration induces heart valve disease in rats.

Abstract

BACKGROUND:

The purpose of this study was to investigate whether rats dosed with serotonin develop changes similar to those seen in human carcinoid heart disease.

METHODS AND RESULTS:

Ten Sprague-Dawley rats were given serotonin injections subcutaneously once daily for 3 months; controls were given saline. A long-lasting hyperserotoninemia with a >10-fold increase in both platelet-poor plasma and dialysate from the femoral muscles appeared. The animals developed clinical signs such as flushing and loose stools. After 3 months, 6 of 10 rats given serotonin had pathological echocardiographs. Two animals had a combination of aortic and pulmonary valve insufficiency, 1 had isolated aortic valve insufficiency, and 3 had isolated pulmonary valve insufficiency. Histopathological examination revealed shortened and thickened aortic cusps and carcinoidlike plaques characterized by a collection of myofibroblasts within an extracellular matrix of collagen ground substance. Immunostaining for Ki-67 demonstrated an increased number of proliferating subendocardial cells. In the control group, no pathological changes were seen. With the use of reverse-transcription polymerase chain reaction, normal rat aortic cusps were shown to express mRNA for serotonin receptors 5-HT1A, 5-HT2A, and 5-HT2B and the serotonin transporter 5-HTT.

CONCLUSIONS:

For the first time, long-term serotonin administration was performed in rats. Morphological and echocardiographic changes similar to those seen in human carcinoid heart disease developed. This study demonstrates that serotonin most likely is involved in the pathogenesis of carcinoid heart disease.

• Authors: Björn I Gustafsson, Karin Tømmerås, Ivar Nordrum, Jan P Loennechen, Anders Brunsvik, Erik Solligård, Reidar Fossmark, Ingunn Bakke, Unni Syversen, Helge Waldum
• Journal: Circulation (Circulation) Vol. 111 Issue 12 Pg. 1517-22 (Mar 29 2005) ISSN: 1524-4539 [Electronic] United States
• PMID: 15781732 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ki-67 Antigen
• Membrane Glycoproteins
• Membrane Transport Proteins
• Nerve Tissue Proteins
• RNA, Messenger
• Receptors, Serotonin
• Serotonin Plasma Membrane Transport Proteins
• Slc6a4 protein, rat
• Serotonin

Topics

• Animals
• Carcinoid Heart Disease (chemically induced, pathology, physiopathology)
• Disease Models, Animal
• Electrocardiography
• Extracellular Matrix (chemistry)
• Fibroblasts (pathology)
• Heart Valve Diseases (chemically induced, pathology)
• Ki-67 Antigen (analysis)
• Membrane Glycoproteins (genetics)
• Membrane Transport Proteins (genetics)
• Nerve Tissue Proteins (genetics)
• RNA, Messenger (analysis)
• Rats
• Rats, Sprague-Dawley
• Receptors, Serotonin (genetics)
• Serotonin (administration & dosage, blood, pharmacology)
• Serotonin Plasma Membrane Transport Proteins
• Time Factors