Cyproheptadine prevents pergolide-induced valvulopathy in rats: an echocardiographic and histopathological study
Open Access
- 1 June 2009
- journal article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 296 (6), H1940-H1948
- https://doi.org/10.1152/ajpheart.01177.2008
Abstract
Serotonergic drugs, such as pergolide, have been associated with the development of cardiac valvular myxoid thickening and regurgitation in humans and more recently in rats. These effects are potentially mediated by the 5-hydroxytryptamine (5-HT)2B receptor (5-HT2BR). Therefore, we sought to determine whether cyproheptadine, a 5-HT2BR antagonist, might prevent toxic valvulopathy in an animal model of pergolide-induced valvular heart disease. For this purpose, 50 male Wistar rats received daily intraperitoneal injections of pergolide (0.5 mg/kg, n = 14), pergolide (0.5 mg/kg) combined with cyproheptadine (10 mg/kg, n = 12), cyproheptadine (10 mg/kg, n = 12), or no injections (control, n = 12) for 20 wk. Echocardiography was performed blindly at baseline and at 10 and 20 wk followed by pathology. At baseline, no differences between groups were found with echocardiography. At 20 wk, aortic regurgitation was present in all pergolide-treated animals, whereas it was less frequently observed in the other groups ( P < 0.0001). For the other valves, this difference was less pronounced. On histopathology, not only aortic but also mitral valves were thicker, myxoid, and exhibited more 5-HT2BR-positive cells in pergolide-treated animals compared with the other groups. Moreover, regurgitant aortic and mitral valves were thicker than nonregurgitant aortic and mitral valves. In conclusion, we found that cyproheptadine prevented pergolide-induced valvulopathy in rats, which was associated with a reduced number of 5-HT2BR-positive valvular cells. This may have important clinical implications for the prevention of serotonergic drug-induced valvular heart disease.Keywords
This publication has 32 references indexed in Scilit:
- Serotonin 5-HT 2B Receptor Blockade Prevents Reactive Oxygen Species–Induced Cardiac Hypertrophy in MiceHypertension, 2008
- 5-Hydroxytryptamine (5HT)-induced valvulopathy: Compositional valvular alterations are associated with 5HT2B receptor and 5HT transporter transcript changes in Sprague-Dawley ratsExperimental and Toxicologic Pathology, 2008
- In vivo model of drug-induced valvular heart disease in rats: pergolide-induced valvular heart disease demonstrated with echocardiography and correlation with pathologyEuropean Heart Journal, 2007
- Drugs and Valvular Heart DiseaseThe New England Journal of Medicine, 2007
- Evaluation of glycosaminoglycans content and 5-hydroxytryptamine 2B receptor in the heart valves of Sprague-Dawley rats with spontaneous mitral valvulopathy – A possible exacerbation by dl-amphetamine sulfate in Fischer 344 rats?Experimental and Toxicologic Pathology, 2006
- Involvement of the Serotonin 5-HT 2B Receptor in Cardiac Hypertrophy Linked to Sympathetic StimulationCirculation, 2004
- 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”) Induces Fenfluramine-Like Proliferative Actions on Human Cardiac Valvular Interstitial Cells in VitroMolecular Pharmacology, 2003
- Endocardial Myxomatous Change in Harlan Sprague-Dawley Rats (Hsd:S—D) and CD-1 Mice: Its Microscopic Resemblance to Drug-Induced Valvulopathy in HumansToxicologic Pathology, 2002
- Valvular Heart Disease Associated with Fenfluramine–PhentermineThe New England Journal of Medicine, 1997
- A study of cyproheptadine in the treatment of metastatic carcinoid tumor and the malignant carcinoid syndromeCancer, 1991