LF 16-0687 Ms, a new bradykinin B2 receptor antagonist, decreases ex vivo brain tissue prostaglandin E2 synthesis after closed head trauma in rats.
OBJECTIVE
Bradykinin (B) contributes to secondary brain injury. This injury is mediated in part by prostaglandin (PG). Antagonism of B(2) receptors improves neurological status after brain injury, but the effect of B(2) antagonism on brain tissue PG is unknown. This study examined the effect of LF 16-0687 Ms, a new B(2) receptor antagonist, on brain tissue PGE(2) after closed head trauma (CHT).


METHODS
Rats were anesthetized and received sham+saline, sham+LF 16-0687 Ms, CHT+saline, or CHT+LF 16-0687 Ms. Brain tissue samples were obtained at 24 h for determination of PGE(2) (after 2 h of ex vivo incubation) and water content. Neurological severity score (NSS) was assessed at 1 and 24 h.


RESULTS
In the group receiving CHT+LF 16-0687 Ms, brain tissue PGE(2) (77.7+/-65.9 pg/mg tissue, mean+/-SD) was less than in the group receiving CHT+saline (368.1+/-186.2 pg/mg tissue) and not different than sham+saline (78.7+/-30.7 pg/mg tissue). LF 16-0687 Ms also improved NSS and decreased brain water content by 51%.


CONCLUSIONS
We conclude that the beneficial effect of LF 16-0687 Ms on outcome after CHT is accompanied by blockade of PGE(2) increase in injured brain tissue.
Kaplanski
Jakob
J
Department of Pharmacology, Faculty of Health Sciences, Soroka Medical Center, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel.
Asa
Ilia
I
Artru
Alan A
AA
Azez
Abed
A
Ivashkova
Yulia
Y
Rudich
Zvia
Z
Pruneau
Didier
D
Shapira
Yoram
Y
D000818:Animals; D065168:Bradykinin Receptor Antagonists; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D046508:Culture Techniques; D015232:Dinoprostone / Q000032:analysis / Q000096:biosynthesis*; D004195:Disease Models, Animal; D016489:Head Injuries, Closed / Q000378:metabolism*; D007427:Intracranial Pressure / Q000187:drug effects; D008297:Male; D015999:Multivariate Analysis; D011336:Probability; D011804:Quinolines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D018709:Statistics, Nonparametric
D065168:Bradykinin Receptor Antagonists; C403051:LF 16-0687; D011804:Quinolines; D015232:Dinoprostone