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This Article Full Text Full Text (PDF) All Versions of this Article: 583/3/1129    most recent jphysiol.2007.139592v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Frithiof, R. Articles by Rundgren, M. Search for Related Content PubMed PubMed Citation Articles by Frithiof, R. Articles by Rundgren, M. Related Collections Integrative

¹ Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

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 (AT₁), 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, AT₁ 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 (m²)^–1 versus +0.9 l min^–1 (m²)^–1 (Man) and +0.9 l min^–1 (m²)^–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 AT₁ receptors contribute, together with plasma volume expansion, to improve systemic haemodynamics after treatment with hypertonic NaCl in haemorrhagic hypovolaemia.

(Received 27 June 2007; accepted after revision 14 July 2007; first published online 19 July 2007)
Corresponding author R. Frithiof: Department of Physiology and Pharmacology, Karolinska Institutet, S-17177, Stockholm, Sweden. Email: robert.frithiof{at}ki.se