An inhibitor of angiotensin converting enzyme (enalapril) augments endotoxin-induced hypotension in the pig.
Septic shock causes an extensive inflammatory reaction including increased capillary leakage and a decrease in systemic blood pressure. Human septic shock can be replicated in the endotoxaemic pig. Angiotensin converting enzyme (ACE) is involved in the degradation of bradykinin, an inflammatory mediator, and in the regulation of blood pressure. Inhibition of ACE is a common approach to reduce hypertension as well as left ventricular insufficiency. Fifteen anaesthetised pigs received a continuous 3 h endotoxin infusion. The animals were randomly given an inhibitor of ACE (enalpril) [at a dose (0.5 mg x kg-1) that did not per se reduce mean arterial blood pressure (MAP); (n = 7)], or the corresponding volume of saline (n = 8). Another seven pigs were randomised for treatment with enalapril (0.5 mg x kg-1) + saline (n = 3). Four pigs were randomised to serve as untreated controls (saline + saline). Basic physiologic variables were registered. Endotoxaemia progressively reduced MAP. This decrease was significantly augmented by enalapril. Hypovolemia caused by increased permeability or salt/water excretion did not seem to explain this effect as neither blood haemoglobin nor plasma sodium differed between the two groups of endotoxaemic pigs. Inhibitors of ACE are known to potentiate the cardio-depressant effect of bradykinin. This may explain the reduction in MAP by enalapril during porcine endotoxaemia.
Kiiski
R
R
Department of Anaesthesia, University Hospital of Uppsala, Sweden.
Hänni
I A
IA
Larsson
A
A
Nordgren
A
A
Carlstedt
F
F
Eriksson
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D004656:Enalapril / Q000494:pharmacology*; D004731:Endotoxins / Q000502:physiology*; D005260:Female; D007022:Hypotension / Q000503:physiopathology*; D008297:Male; D013552:Swine
D000806:Angiotensin-Converting Enzyme Inhibitors; D004731:Endotoxins; C044101:endotoxin, Escherichia coli; D004656:Enalapril