Intravenous hypertonic NaCl acts via cerebral sodium‐sensitive and angiotensinergic mechanisms to improve cardiac function in haemorrhaged conscious sheep

Acute NaCl loading as resuscitation in haemorrhagic hypovolaemia is known to induce rapid cardiovascular recovery. Besides an osmotically induced increase in plasma volume the physiological mechanisms of action are unknown. We hypothesized that a CNS mechanism, elicited by increased periventricular [Na(+)] and mediated by angiotensin II type 1 receptors (AT(1)), is obligatory for the full effect of hypertonic NaCl. To test this we investigated the cardiovascular responses to haemorrhage and subsequent hypertonic NaCl infusion (7.5% NaCl, 4 ml (kg BW)(-1)) in six conscious sheep subjected to intracerebroventricular (i.c.v.) infusion of artificial cerebrospinal fluid (aCSF; control), mannitol solution (Man; 75 mmol l(-1) [Na(+)], total osmolality 295 mosmol kg(-1)) or losartan (Los; 1 mg ml(-1), AT(1) receptor antagonist) at three different occasions. Man normalized (144 +/- 6 mmol l(-1), mean +/- s.d.) the increase in i.c.v. [Na(+)] seen after aCSF (161 +/- 2 mmol l(-1)). Compared with control, both Man and Los significantly (P < 0.05) attenuated the improvement in mean arterial blood pressure (MAP), cardiac index and mesenteric blood flow (SMBF) in response to intravenous hypertonic NaCl: MAP, rapid response +45 mmHg versus +38 mmHg (Man) and +35 mmHg (Los); after 180 min, +32 mmHg versus +21 mmHg (Man) and +19 mmHg (Los); cardiac index after 180 min, +1.9 l min(-1) (m(2))(-1) versus +0.9 l min(-1) (m(2))(-1) (Man) and +0.9 l min(-1) (m(2))(-1) (Los); SMBF rapid response, +981 ml min(-1) versus +719 ml min(-1) (Man) and +744 ml min(-1) (Los); after 180 min, +602 ml min(-1) versus +372 ml min(-1) (Man) and +314 ml min(-1) (Los). The results suggest that increased periventricular [Na(+)] and cerebral AT(1) receptors contribute, together with plasma volume expansion, to improve systemic haemodynamics after treatment with hypertonic NaCl in haemorrhagic hypovolaemia.