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在麻醉猫中,观察了阿普洛尔(H56 - 28)给药前后,儿茶酚胺输注对心肌血流量、代谢产热及整体血流动力学的影响。

The effect of catecholamine infusions on myocardial blood flow, metabolic heat production and on general haemodynamics, before and after alprenolol (H56-28), in anaesthetized cats.

作者信息

Parratt J R, Wadsworth R M

出版信息

Br J Pharmacol. 1970 May;38(3):554-71. doi: 10.1111/j.1476-5381.1970.tb10597.x.

Abstract
  1. In cats anaesthetized with pentobarbitone sodium, infusions of adrenaline, noradrenaline (0.5 mug/kg per min) and isoprenaline (0.25 mug/kg per min) increased myocardial blood flow, myocardial heat production, left ventricular systolic and end-diastolic pressures, left ventricular +ve and -ve dp/dt max, and calculated cardiac output, effort and oxygen consumption. These effects (apart from the effect of noradrenaline on left ventricular systolic pressure) were markedly reduced by previous administration of alprenolol (0.5 or 1.0 mg/kg).2. Infusions of adrenaline and noradrenaline increased arterial diastolic blood pressure and isoprenaline reduced it. After alprenolol the effects of adrenaline and noradrenaline were potentiated and that of isoprenaline abolished; in some experiments isoprenaline increased arterial diastolic pressure after alprenolol. Alprenolol did not influence the increases in arterial systolic pressure which followed the administration of adrenaline and noradrenaline.3. Isoprenaline-induced tachycardia was markedly reduced and adrenaline tachycardia was converted to bradycardia after alprenolol. The bradycardia which occurred during noradrenaline infusions was unaffected.4. After blockade by alprenolol, recovery of the effects of isoprenaline on left ventricular dp/dt and on heart rate occurred more quickly than recovery of the effects on arterial diastolic pressure. This suggests that alprenolol has a greater affinity for beta(2)- than for beta(1)-adrenoceptors.5. Intravenous administration of acetylcholine decreased arterial blood pressure, left ventricular pressure and +ve and -ve dp/dt max. During recovery from these effects there was a marked increase in +ve dp/dt max. which was absent after the administration of alprenolol (0.5 mg/kg). Because this dose of alprenolol is thus able to block the effects of reflex sympathetic cardiac nerve stimulation but does not completely antagonize the effects of exogenous adrenaline on dp/dt, it is suggested that alprenolol may have some adrenergic neurone blocking activity.6. Increases in liver and myocardial blood flow and heat production produced by noradrenaline, adrenaline and isoprenaline were reduced after alprenolol.7. Isoprenaline reduced air-way resistance and this effect was abolished by alprenolol; increases in air-way resistance produced by adrenaline and nor-adrenaline were augmented. All three amines inhibited intestinal smooth muscle contractions in vivo. Only the effect of isoprenaline was reduced by alprenolol.
摘要
  1. 在用戊巴比妥钠麻醉的猫中,输注肾上腺素、去甲肾上腺素(0.5微克/千克每分钟)和异丙肾上腺素(0.25微克/千克每分钟)可增加心肌血流量、心肌产热、左心室收缩压和舒张末期压力、左心室最大正负dp/dt,并计算心输出量、作功和氧耗。预先给予阿普洛尔(0.5或1.0毫克/千克)可使这些效应(除去甲肾上腺素对左心室收缩压的效应外)明显减弱。

  2. 输注肾上腺素和去甲肾上腺素可使动脉舒张压升高,而异丙肾上腺素则使其降低。给予阿普洛尔后,肾上腺素和去甲肾上腺素的效应增强,而异丙肾上腺素的效应则消失;在一些实验中,给予阿普洛尔后异丙肾上腺素可使动脉舒张压升高。阿普洛尔不影响给予肾上腺素和去甲肾上腺素后动脉收缩压的升高。

  3. 给予阿普洛尔后,异丙肾上腺素诱发的心动过速明显减弱,肾上腺素诱发的心动过速转变为心动过缓。去甲肾上腺素输注期间出现的心动过缓不受影响。

  4. 经阿普洛尔阻断后,异丙肾上腺素对左心室dp/dt和心率的效应恢复比其对动脉舒张压的效应恢复更快。这表明阿普洛尔对β₂肾上腺素能受体的亲和力比对β₁肾上腺素能受体的亲和力更大。

  5. 静脉注射乙酰胆碱可降低动脉血压、左心室压力以及最大正负dp/dt。从这些效应恢复期间,最大正dp/dt有明显增加,而给予阿普洛尔(0.5毫克/千克)后则无此现象。由于该剂量的阿普洛尔能够阻断反射性交感神经心脏神经刺激的效应,但不能完全拮抗外源性肾上腺素对dp/dt的效应,因此提示阿普洛尔可能具有一些肾上腺素能神经元阻断活性。

  6. 给予阿普洛尔后,去甲肾上腺素、肾上腺素和异丙肾上腺素所引起的肝脏和心肌血流量及产热增加均减弱。

  7. 异丙肾上腺素可降低气道阻力,此效应被阿普洛尔消除;肾上腺素和去甲肾上腺素所引起的气道阻力增加则增强。所有三种胺类均在体内抑制肠道平滑肌收缩。只有异丙肾上腺素的效应被阿普洛尔减弱。

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