Intracerebroventricular angiotensin II increases tolerance to blood loss in conscious sheep

Intracerebroventricular (i.c.v.) infusion of hypertonic NaCl improves the tolerance to haemorrhage in sheep. Since i.c.v. angiotensin II (ANG II) shares many of the effects of hypertonic NaCl on fluid balance control and blood pressure, we aimed to determine whether i.c.v. ANG II would also be effective in that regard. Six adult conscious ewes were bled from the jugular vein until the mean arterial pressure suddenly dropped to between 45 and 50 mmHg, during an i.c.v. infusion of ANG II (2 pmol kg-1 min-1) which commenced 30 min prior to start of blood removal and continued until end of retransfusion about 80 min after haemorrhage. A corresponding haemorrhage in the same animals during an i.c.v. infusion of 0.9% NaCl served as controls. Significantly more blood had to be withdrawn to induce hypotension when ANG II was given i.c.v. (22.3 +/- 1.8 vs. 12.6 +/- 1.2 mL kg-1). The degree of hypotension and the recovery rate of the blood pressure did not differ between the experiments. The increased tolerance to blood loss by ANG II i.c.v. was accompanied by a reinforced elevation of the systemic vascular resistance and a larger decline of the cardiac output. The plasma norepinephrine concentration was significantly increased immediately after haemorrhage during i.c.v. ANG II, but not in control experiments. The overall vasopressin response to the hypotensive blood loss was not affected by ANG II, but high plasma levels were obtained already during the non-hypotensive stage of haemorrhage. The i.c.v. infusion of ANG II caused a significant lowering of the plasma protein concentration before start of bleeding and accentuated the haemodilution caused by the haemorrhage. We conclude that central administration of ANG II increases the tolerance to haemorrhage in sheep but with concomitant haemodynamic changes which appear unfavourable regarding cardiac load and tissue perfusion.