Effect of angiotensin II and endothelin‐1 receptor blockade on the haemodynamic and hormonal changes after acute blood loss and after retransfusion in conscious dogs

Publisher Website
Google Scholar
Abstract
Aim:  This study investigates angiotensin II and endothelin‐1 mediated mechanisms involved in the haemodynamic, hormonal, and renal response towards acute hypotensive haemorrhage.Methods:  Conscious dogs were pre‐treated with angiotensin II type 1 (AT1) and/or endothelin‐A (ETA) receptor blockers or not. Protocol 1: After a 60‐min baseline period, 25% of the dog's blood was rapidly withdrawn. The blood was retransfused 60 min later and data recorded for another hour. Protocol 2: Likewise, but preceded by AT1 blockade with i.v. Losartan. Protocol 3: Likewise, but preceded by ETA blockade with i.v. ABT‐627. Protocol 4: Likewise, but with combined AT1plus ETAblockade.Results:  In controls, haemorrhage decreased mean arterial pressure (MAP) by approximately 25%, cardiac output by approximately 40%, and urine volume by approximately 60%, increased angiotensin II (3.1‐fold), endothelin‐1 (1.13‐fold), vasopressin (116‐fold), and adrenaline concentrations (3.2‐fold). Glomerular filtration rate and noradrenaline concentrations remained unchanged. During AT1 blockade, the MAP decrease was exaggerated (−40%) and glomerular filtration rate fell. During ETA blockade, noradrenaline increased after haemorrhage instead of adrenaline, and the MAP recovery after retransfusion was blunted. The decrease in cardiac output was similar in all protocols.Conclusions:  Angiotensin II is more important than endothelin‐1 for the short‐term regulation of MAP and glomerular filtration rate after haemorrhage, whereas endothelin‐1 seems necessary for complete MAP recovery after retransfusion. After haemorrhage, endothelin‐1 seems to facilitate adrenaline release and to blunt noradrenaline release. Haemorrhage‐induced compensatory mechanisms maintain blood flow more effectively than blood pressure, as the decrease in cardiac output – but not MAP – was similar in all protocols.