期刊
POULTRY SCIENCE
卷 85, 期 4, 页码 777-786出版社
ELSEVIER
DOI: 10.1093/ps/85.4.777
关键词
pulmonary hypertension; broiler; serotonin; ketanserin; methiothepin
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-HT1B/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-HT1/2 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 A(2) 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.
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