| There is not much information about the effects of endothelin-1 (ET-1), a potent endogenous constrictor of vascular, on haemodynamics or which ET receptor subtypes mediate ET-1-induced vasoconstrictive action in the poultry. ET-1 not only causes a potent and prolonged vasoconstriction but also are known to enhance cell proliferation and to stimulate extracellular matrix accumulation in vivo and in vitro. To clarify the actions of ET-1 underlying pulmonary circulation and systemic circulation in poultry, we investigated the effect of ET-1, BQ123 (a selective ETA receptor antagonist) and ET-1 antibody (ET-1 Ab) on the pulmonary arterial contract pressure (PACP), pulmonary arterial stretch pressure (PASP), femoral arterial contract pressure (FACP), femoral arterial stretch pressure (FASP), right ventricular systolic pressure (RVSP), the maximum increasing rate of right ventricular (RV+dp/dt), heart rate (HR) in normal laying-egg chickens, broilers with and without pulmonary hypertension (PH). We also studied the effects of long-term BQ-123 treatment on the broilers exposed to low ambient temperatures.1. ET-1 produced dose-dependent increases in PACP, PASP, FACP, FASP, RVSP, RVDP, which were rapidly decreases in onset preceded sustained biphasic ascending (first phase peaking at 1-2 minutes; second phase peaking at 10-15 minutes) after injecting 1.0 and 2.0 ug/kg ET-1 through wing veins, whereas, decreases of RV+dp/dt and HR were observed. No distinctness was found between the laying-egg chickens and broilers and there are more change in pulmonary than systemic circulation in either bird.2. ET-1 Ab (1:2500) (i.v) caused descending in PACP, PASP, FACP, FASP, RVSP, and a little ascending in RV+dp/dt and HR. The results revealed that pulmonary vessels are more sensitive to ET-1-induced vasoconstriction than systemic vessels and showed endogenous ET-1 is responsible for the basic balance of blood pressure in chicks.3. 2.0 ug/kg BQ123 (i.v.) induced PACP, PASP, FACP, FASP, RVSP increase and RV+dp/dt, HR decrease more significantly than 0.4 ug/kg BQ123, whereas, there was no evident change in saline control. These results suggest that ET-1 ?ETAR play an important role in the regulation of in systemic and pulmonary circulations.4. That much fewer increases in PACP, PASP, FACP, FASP were caused by 2.0 ug/kg ET-1 (i.v.) in broilers with PH induced by low ambient temperatures than normal broilers indicates there is some change of ET-1 in the development of PH in broilers.5. That ET-1 Ab (1:2500) induced more decreases of PACP, PASP in broiler with pulmonary hypertension induced by low ambient temperatures than the normal ones but not FACP, FASP suggestsET-1 take part in the development of PH in broilers.6. The much more decreases of PACP, PASP, FACP, FASP induced by BQ123 (2.0 ng/kg, i.v;) in PH broilers than normal broilers also demonstrates the impdrtance of ET-l in the development of PH in broilers.7. Long-term (14 days) BQ-123 pretreatment greatly prevented pulmonary hypertension in the broilers exposed in low ambient temperatures (LAT), while LAT led to severe PH in saline and blank groups accompanied by increases in RVSP, PCV, AHI, HR and a decrease in RV |dp/dt|. All these suggest that endothelin-1 play an important role in the development of pulmonary hypertension caused by LAT and that BQ123 ( an ETAR antagonist) may be a new therapeutic agent for LAT-induced pulmonary hypertension in broilers.The study demonstrates considerable similarities in the complex haemodynamic effects of ET-l in chicks. ET-l is one of the factors that regulate the blood vessels rhythm of normal chicks., The study Also indicates ET-l play an important role in development of PH in broilers and BQ123 can prevent PH. Accordingly Future studies are needed to show whether desensitization or upregulation/downregulation of the ETAR may contribute to the increase in circulating ET-l levels in pulmonary hypertension in broilers. The blockage of the ETAR pathway by BQ123 is,a new way to reduce... |
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