Aminoguanidine reduces brain lesion volume after cold injury in the rat.
The aim of this study was to examine the effect of aminoguanidine (AG), which is thought to be an inducible nitric oxide synthase (iNOS) inhibitor, on lesion volume induced by cold injury in the parietal cortex of the rat. Cold lesion was induced by applying a precooled (-78 degrees C) copper cylinder (diameter: 3 mm) for 6 s to the intact dura. Lesion volume was determined using the triphenyltetrazolium-chloride method after 24 h. Pretreatment (1 h) and posttreatment (7.5 h) with AG [10 or 100 mg/kg body mass (BM)] reduced the lesion volume by 15 and 27%, respectively. However, posttreatment alone with AG (10 and 100 mg/kg BM) caused less of a reduction in lesion volume, by 8 and 20%, respectively. Pre- and posttreatment with AG also reduced the plasma nitrate/nitrite concentration compared with lesioned, saline-treated rats. Only a double therapy with AG (100 mg/kg BM) resulted in a significant reduction (48%) compared to saline alone, which was even larger (55%) compared to the sham group. The tissue nitrate/ nitrite concentration was significantly attenuated by pre- and posttreatment with AG (100 mg/kg BM) not only in the ipsilateral but also in the contralateral hemisphere. There was no difference regarding the parameter between shams and lesioned, saline-treated rats. Since combined pre- and posttreatment with AG reduced the lesion volume more than posttreatment alone and the plasma and tissue nitrate/nitrite concentrations were diminished during AG therapy compared to shams, we hypothesize that AG inhibits not only iNOS but also other enzymes, such as nNOS, diamine oxidase, and advanced glycation endproducts synthase.
Görlach
C
C
Department of Physiology, Ludwig-Maximilians University Munich, Germany. C.Goerlach@lrz.uni-muenchen.de
Hortobágyi
T
T
Benyó
Z
Z
Wahl
M
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D003080:Cold Temperature; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D009566:Nitrates / Q000097:blood / Q000378:metabolism; D009573:Nitrites / Q000097:blood / Q000378:metabolism; D009994:Osmolar Concentration; D051381:Rats; D011921:Rats, Inbred WKY
D004791:Enzyme Inhibitors; D006146:Guanidines; D009566:Nitrates; D009573:Nitrites; C004479:pimagedine