Evaluation of the serotonin receptor blockers ketanserin and methiothepin on the pulmonary hypertensive responses of broilers to intravenously infused serotonin

• Published in: Poultry science 2006-04, Vol.85 (4), p.777-786
• Main Authors: Chapman, M.E, Wideman, R.F. Jr
• Format: Article
• Language: English
• Subjects: Animals; ascites; Blood Pressure - drug effects; Chickens; hypertension; Hypertension, Pulmonary - chemically induced; Hypertension, Pulmonary - drug therapy; Hypertension, Pulmonary - physiopathology; Hypertension, Pulmonary - veterinary; Injections, Intravenous; Ketanserin - pharmacology; Male; Methiothepin - pharmacology; pathogenesis; Poultry Diseases - chemically induced; Poultry Diseases - drug therapy; Poultry Diseases - physiopathology; Prostaglandin Endoperoxides, Synthetic - pharmacology; Receptors, Serotonin, 5-HT1 - metabolism; Receptors, Serotonin, 5-HT2 - metabolism; Serotonin - administration & dosage; Serotonin - pharmacology; Serotonin 5-HT1 Receptor Antagonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists - pharmacology; vasoconstriction; vasodilator agents
• ISSN: 0032-5791; 1525-3171
• DOI: 10.1093/ps/85.4.777

The pathogenesis of pulmonary hypertension remains incompletely understood. Many factors have been implicated; however, there has been great interest in the potent pulmonary vasoconstrictor serotonin (5-HT) due to episodes of primary pulmonary hypertension in humans triggered by serotoninergic appetite-suppressant drugs. Pulmonary hypertensive patients have elevated blood 5-HT levels and pulmonary vasoconstriction induced by 5-HT is believed to be mediated through 5-HT(1B/1D) and 5-HT2A receptors that are expressed by pulmonary smooth muscle cells. The vascular remodeling associated with pulmonary hypertension also appears to require the serotonin transporter. We investigated the roles of 5-HT receptor blockers on the development of pulmonary hypertension induced by infusing 5-HT i.v. in broilers. For this purpose, we treated broilers with the selective 5-HT2A receptor antagonist ketanserin (5 mg/kg of BW) or with the nonselective 5-HT(1/2) receptor antagonist methiothepin (3 mg/kg of BW). Receptor blockade was followed by infusion of 5-HT while recording pulmonary arterial pressure and pulmonary arterial blood flow. The results demonstrate that methiothepin, but not ketanserin, eliminated the 5-HT-induced pulmonary hypertensive responses in broilers. The 5-HT2A receptor does not, therefore, appear to play a role in the 5-HT-induced pulmonary hypertensive responses in broilers. Methiothepin did not inhibit pulmonary vascular contractility per se, because the pulmonary hypertensive response to the thromboxane A2 mimetic U44069 remained intact in methiothepin-treated broilers. Methiothepin will be a useful tool for evaluating the role of 5-HT in the pathogenesis of pulmonary hypertension syndrome (ascites) as well as the onset of pulmonary hypertension triggered by inflammatory stimuli such as bacterial lipolysaccharide.