Mathai M L, Pennington G L, McKinley M J
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
Acta Physiol Scand. 1997 Dec;161(4):495-502. doi: 10.1046/j.1365-201X.1997.00266.x.
The effect of systemic or intracerebroventricular (ICV) infusion of the angiotensin AT1 receptor antagonist losartan on blood pressure during hypotensive haemorrhage was investigated in five conscious sheep. Mean arterial pressure (MAP) was measured during haemorrhage (15 mL kg-1 body wt). Losartan (1 or 0.33 mg h-1) was given to sheep by ICV, intravenous or intracarotid administration, beginning 60 min before and continuing during the haemorrhage. During control infusion of ICV artificial cerebrospinal fluid, MAP was maintained until 13.16 +/- 0.84 mL kg-1 blood loss, when a rapid reduction of at least 15 mmHg in arterial pressure occurred (the decompensation phase). ICV infusion of losartan at 1 mg h-1 caused an early onset of the decompensation phase after only 9.8 +/- 0.8 mL kg-1 of blood loss compared with control. Intravenous infusion of losartan (1 mg h-1) also caused an early onset (P < 0.05) of the decompensation phase at 10.2 +/- 1.0 mL kg-1 blood loss. This dose of losartan inhibited the pressor response to ICV angiotensin II, but not to intravenously administered angiotensin II, indicating that only central AT1 receptors were blocked. Bilateral carotid arterial administration of losartan at 0.33 mg h-1 caused an early onset of the decompensation phase during haemorrhage at 11.06 +/- 0.91 mL kg-1 blood loss (P < 0.05), which did not occur when infused by intravenous or ICV routes. The results indicate that an angiotensin AT1-receptor-mediated mechanism is involved in the maintenance of MAP during haemorrhage in sheep. The locus of this mechanism appears to be the brain.
在五只清醒的绵羊中研究了全身或脑室内（ICV）注入血管紧张素AT1受体拮抗剂氯沙坦对低血压性出血期间血压的影响。在出血（15 mL/kg体重）期间测量平均动脉压（MAP）。在出血前60分钟开始并在出血期间持续通过ICV、静脉内或颈内动脉给药给予绵羊氯沙坦（1或0.33 mg/h）。在ICV人工脑脊液的对照输注期间，MAP维持到失血13.16±0.84 mL/kg时，动脉压迅速降低至少15 mmHg（失代偿期）。与对照相比，以1 mg/h的剂量ICV注入氯沙坦仅在失血9.8±0.8 mL/kg后就导致失代偿期提前出现。静脉内注入氯沙坦（1 mg/h）也在失血10.2±1.0 mL/kg时导致失代偿期提前出现（P<0.05）。该剂量的氯沙坦抑制了对ICV血管紧张素II的升压反应，但不抑制对静脉内给予的血管紧张素II的反应，表明仅中枢AT1受体被阻断。以0.33 mg/h的剂量双侧颈内动脉给药氯沙坦在失血11.06±0.91 mL/kg时导致出血期间失代偿期提前出现（P<0.05），而通过静脉内或ICV途径输注时未出现这种情况。结果表明，血管紧张素AT1受体介导的机制参与绵羊出血期间MAP的维持。该机制的位点似乎在脑内。
