Does losartan prevent cerebral edema? A preliminary study using a vascular compartment model.
BACKGROUND
The purpose of this study was to ascertain the effect of Losartan, a non-peptide angiotensin II receptor antagonist used for the treatment of hypertension, on the movement of proteins and fluids across the vascular compartment in ischemic cat brains.


METHODS
The experiments were carried out on anesthetized cats under artificial ventilation and autohemoperfusion of the brain with a stable volume of blood with the help of a resistograph. Cerebral ischemia was induced by a 15-minute arrest of the autohemoperfusion pump, tying various anastomoses in the neck region, and reducing arterial pressure to 40-30 mm Hg by hemorrhage with subsequent reinfusion of the lost blood.


RESULTS
In the postischemic period in the cat brain, control experiments showed the onset of metabolic acidosis and an increase in permeability of the brain capillaries to fluids and protein molecules. Intravenous introduction of losartan, an angiotensin II receptor antagonist, at a dose of 3 mg x kg(-1) 10 minutes into the postischaemic period, enhanced the normalization of metabolic and transcapillary exchange. Thus vector permeability was reversed from blood-to-tissue in the control situation (without losartan) to tissue-to-blood during losartan administration.


CONCLUSIONS
The results provide strong evidence that losartan may play a role in preventing cerebral edema, and that the renin-angiotensin system plays an important role in postischemic cerebrovascular events.
Asiedu-Gyekye
Isaac Julius
IJ
Department of Pharmacology, University of Ghana Medical School, Accra, Ghana. asiedugyekye@yahoo.co.uk
Antwi
Daniel A
DA
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D002199:Capillary Permeability / Q000187:drug effects; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008955:Models, Cardiovascular; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D001798:Blood Proteins; D019808:Losartan