Oyekan A O, Botting J H
Pharmacology Group, King's College, University of London, United Kingdom.
Cardiovasc Res. 1991 May;25(5):431-7. doi: 10.1093/cvr/25.5.431.
The aim was to determine the receptors involved in the antiaggregatory effects of adrenaline in the rat.
The 111indium oxine technique was used to evaluate ADP induced pulmonary accumulation of 111In labelled platelets in adrenalectomised rats (ie, no endogenous adrenaline) in the absence of anticoagulants. Adrenaline was infused (10, 20 and 40 micrograms.kg-1.h-1) and ADP aggregation measured. Adrenoceptor agonists, isoprenaline, methoxamine, and BHT 933, were given to evaluate whether they mimic the adrenaline effects. Adrenoceptor antagonists, yohimbine, propranolol, prazosin, and WY 26392, were given to assess whether they block the adrenaline effects.
In all cases, pulmonary accumulation of platelets was measured in response to ADP. Adrenaline dose dependently inhibited platelet aggregation. BHT 933 (1.5 micrograms.kg-1.min-1) mimicked, while phentolamine (1 mg.kg-1), yohimbine (2.5 mg.kg-1), and WY 26392 (0.1, 1.0, 5.0 mg.kg-1) blocked, the adrenaline effects. Methoxamine (3.3 micrograms.kg-1.min-1) produced a relatively weak non-specific inhibition of ADP aggregation. Isoprenaline (33 ng.kg-1.min-1) did not mimic the effects of adrenaline, neither did propranolol (1 mg.kg-1) affect the adrenaline inhibition of the aggregatory responses to ADP. Indomethacin (3 mg.kg-1) blocked the inhibitory effects of adrenaline.
Adrenaline stimulates alpha receptors on platelets but inhibits platelet aggregation. There is no evidence to suggest that beta receptors participated in the effects produced by adrenaline. There is a role for cyclo-oxygenase products in the inhibitory effects of adrenaline on aggregation.
本研究旨在确定大鼠体内参与肾上腺素抗聚集作用的受体。
采用111铟氧肟酸盐技术,在无抗凝剂的情况下,评估肾上腺素对去肾上腺大鼠(即无内源性肾上腺素)体内由二磷酸腺苷(ADP)诱导的111铟标记血小板在肺部的聚集情况。静脉输注肾上腺素(10、20和40微克·千克-1·小时-1),并测量ADP诱导的血小板聚集。给予肾上腺素能受体激动剂异丙肾上腺素、甲氧明和BHT 933,以评估它们是否模拟肾上腺素的作用。给予肾上腺素能受体拮抗剂育亨宾、普萘洛尔、哌唑嗪和WY 26392,以评估它们是否阻断肾上腺素的作用。
在所有情况下,均测量了ADP诱导的血小板在肺部的聚集情况。肾上腺素呈剂量依赖性地抑制血小板聚集。BHT 933(1.5微克·千克-1·分钟-1)模拟了肾上腺素的作用,而酚妥拉明(1毫克·千克-1)、育亨宾(2.5毫克·千克-1)和WY 26392(0.1、1.0、5.0毫克·千克-1)阻断了肾上腺素的作用。甲氧明(3.3微克·千克-1·分钟-1)对ADP诱导的血小板聚集产生相对较弱的非特异性抑制作用。异丙肾上腺素(33纳克·千克-1·分钟-1)未模拟肾上腺素的作用,普萘洛尔(1毫克·千克-1)也未影响肾上腺素对ADP诱导的血小板聚集反应的抑制作用。吲哚美辛(3毫克·千克-1)阻断了肾上腺素对血小板聚集的抑制作用。
肾上腺素刺激血小板上的α受体,但抑制血小板聚集。没有证据表明β受体参与了肾上腺素产生的效应。环氧化酶产物在肾上腺素对血小板聚集的抑制作用中发挥作用。