Doursout M F, Chelly J E, Hartley C J, Szilagyi J, Montastruc J L, Buckley J P
Department of Anesthesiology, Baylor College of Medicine, Houston, Texas.
J Pharmacol Exp Ther. 1988 Aug;246(2):591-6.
Hemodynamic properties of angiotensin (ANG) II 1, 5, 10 and 100 ng/kg i.v. and 10, 100 and 1000 ng/kg i.v.t. were assessed in conscious dogs. ANG II i.v. produced a dose-dependent pressor response (59 +/- 5-124 +/- 16 mmHg) and renal vasoconstriction (1.3 +/- 0.4-96 +/- 32 mmHg/ml/min). Ganglionic blockade (chlorisondamine 2 mg/kg i.v.) diminished mean arterial responses without altering peptide effects on renal circulation. At the highest dose, ANG II i.v. induced cardiac stimulation: increased heart rate (75 +/- 4-115 +/- 6 beats/min), cardiac output (2.0 +/- 0.1-2.4 +/- 0.2 l/min), dP/dt (2308 +/- 181-2773 +/- 173 mmHg/sec) and coronary blood flow (49 +/- 10-96 +/- 23 ml/min). Although with chlorisondamine cardiac response was more pronounced, subsequent beta blockade abolished it. Concomitantly, an isolated increase in plasma epinephrine was recorded (63 +/- 8-1505 +/- 354 pg/ml). A pressor response (59 +/- 8-89 +/- 13 mmHg) and renal vasoconstriction (1.1 +/- 0.1-2.2 +/- 0.5 mmHg/ml/min) were also produced by ANG II i.v.t. at the highest dose. These centrally mediated changes were prevented by chlorisondamine. Our study demonstrates 1) i.v. ANG II-mediated pressor responses are dependent on direct and indirect components, the relative contribution of each being dependent on the regional circulation; ANG II i.v. also produced a biphasic cardiac response--an initial centrally mediated depression and a secondary stimulation dependent on epinephrine via cardiac beta receptors and 2) i.v.t. ANG II-mediated pressor effects are essentially indirect. Finally, no evidence was found to support the role of vasopressin in ANG II effects.
在清醒犬中评估了静脉注射（i.v.）1、5、10和100 ng/kg以及静脉滴注（i.v.t.）10、100和1000 ng/kg血管紧张素（ANG）II的血流动力学特性。静脉注射ANG II产生剂量依赖性的升压反应（59±5 - 124±16 mmHg）和肾血管收缩（1.3±0.4 - 96±32 mmHg/ml/min）。神经节阻断（静脉注射2 mg/kg氯筒箭毒碱）可减弱平均动脉反应，但不改变肽对肾循环的作用。在最高剂量时，静脉注射ANG II可诱导心脏刺激：心率增加（75±4 - 115±6次/分钟）、心输出量增加（2.0±0.1 - 2.4±0.2 l/分钟）、dp/dt增加（2308±181 - 2773±173 mmHg/秒）和冠状动脉血流量增加（49±10 - 96±23 ml/分钟）。尽管使用氯筒箭毒碱时心脏反应更明显，但随后的β受体阻断可消除该反应。同时，记录到血浆肾上腺素单独升高（63±8 - 1505±354 pg/ml）。静脉滴注ANG II在最高剂量时也产生升压反应（59±8 - 89±13 mmHg）和肾血管收缩（1.1±0.1 - 2.2±0.5 mmHg/ml/min）。这些中枢介导的变化可被氯筒箭毒碱预防。我们的研究表明：1）静脉注射ANG II介导的升压反应依赖于直接和间接成分，每种成分的相对贡献取决于局部循环；静脉注射ANG II还产生双相心脏反应——最初是中枢介导的抑制，继发刺激依赖于通过心脏β受体的肾上腺素；2）静脉滴注ANG II介导的升压作用基本上是间接的。最后，未发现支持血管加压素在ANG II作用中起作用的证据。
