The role of bradykinin in mediating ischemic brain edema in rats.
OBJECTIVE
We investigated the hypothesis that bradykinin generation may induce ischemic brain edema in spontaneously hypertensive rats.


METHODS
Cerebral ischemia lasting 3 hours was produced by bilateral common carotid artery occlusion in 67 rats. After the ischemic period, the rats were reperfused. Cerebral water content and energy metabolites (adenosine triphosphate, lactate, and pyruvate), as well as plasma and tissue bradykinin, were measured. Additionally, using the same experimental paradigm, bradykinin synthesis inhibitors (aprotinin [n = 7] and soybean trypsin inhibitor [n = 7]) were administered immediately after ischemia induction to determine the relation of bradykinin generation to the progression of ischemic brain edema.


RESULTS
Cerebral water content increased during the 3-hour ischemic period, peaked at 30 minutes of reperfusion, and declined thereafter. Bradykinin levels in plasma and tissue rose markedly 30 minutes after reperfusion and fell thereafter. The progressive loss of adenosine triphosphate was mirrored by the rise in lactate. In the treated groups, aprotinin and soybean trypsin inhibitor administration significantly attenuated cerebral edema (p < 0.01 and p < 0.05, respectively). The treated groups also showed less lactate accumulation and more adenosine triphosphate preservation than did the controls.


CONCLUSIONS
These results demonstrate that bradykinin levels in plasma and tissue corresponded to cerebral edema progression and that bradykinin suppression decreased edema formation. These novel findings indicate that bradykinin activation augments the progression of ischemic brain edema.
Kamiya
T
T
Second Department of Internal Medicine, Daiichi Hospital, Nippon Medical School, Tokyo.
Katayama
Y
Y
Kashiwagi
F
F
Terashi
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001794:Blood Pressure; D001834:Body Water / Q000378:metabolism; D001920:Bradykinin / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology*; D002545:Brain Ischemia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000494:pharmacology
D007773:Lactates; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D007611:Aprotinin; D014360:Trypsin Inhibitor, Kunitz Soybean; D001920:Bradykinin