Rat model of depending prostaglandin renal state: effect of ketoprofen.
BACKGROUND
The renal prostaglandins (PGs), vasodilators, preserve kidney function during increased activity of the renin-angiotensin system or renal sympathetic nerves (renal PG-dependent state [RPGD]). Ketoprofen (Ket) inhibits cyclooxygenase and, therefore, the synthesis of PGs. The aim of this study was to determine, in the rat, the action of Ket in the renal histology and function in a RPGD state (stress of anesthesia and hemorrhage).


METHODS
Twenty male Wistar rats, anesthetized with sodium pentobarbital, were randomly divided into two groups: G1--control (n = 10) and G2-Ket (n = 10) submitted to arterial hemorrhage of 30% of volemia (estimated as 6% of body weight) three times (10% each 10 min), 65 min after anesthesia. G2 animals received Ket, 1.5 mg. kg(-1), venously, 5 min after anesthesia and 60 min before the first hemorrhage moment (first moment of the study [M1]). Medium arterial pressure (MAP), rectal temperature (T), and heart rate were monitored. G1 and G2 received para-aminohippurate sodium (PAH) and iothalamate sodium (IOT) solutions during the entire experimental time in order to determine clearance of PAH (effective renal plasma flow [ERPF]) and clearance of IOT (glomerular filtration rate [GFR]) without urine collection (determination of blood concentrations of PAH and IOT through the high-performance liquid chromatography), filtration fraction (FF), and renal vascular resistance (RVR). The animals were sacrificed in M3, 30 min after the third hemorrhage (M2) moment, and the kidneys and blood collected during the hemorrhage periods were utilized for histological study and determinations of hematocrit (Ht), serum creatinine (SCr), ERPF, GFR, FF, and RVR, respectively.


RESULTS
There were significant reductions of MAP, T, and Ht and a significant increase of SCr. During the experiment, ERPF and GFR did not change, but ERPF was always higher in G1 than in G2. Ket did not alter FF, which increased in G1 over the duration of experiment. The Ket group had significantly higher RVR than the control group. The histology verified that both G1 and G2 were similar for tubular dilation and necrosis, but they were significantly different for tubular degeneration: G1 > G2.


CONCLUSIONS
The changes observed in kidney histology probably were determined by hemorrhage and hypotension. Ket inhibited the synthesis of PGs and diminished tubular degeneration.
de Souza Silva
Marcello
M
Department of Anesthesiology, College of Medicine of Botucatu, UNESP-São Paulo State University, SP, Brazil.
Castiglia
Yara Marcondes Machado
YM
Vianna
Pedro Thadeu Galvão
PT
Viero
Rosa Marlene
RM
Braz
José Reinaldo Cerqueira
JR
Cassetari
Maria Luiza
ML
D000758:Anesthesia; D000818:Animals; D016063:Blood Loss, Surgical / Q000503:physiopathology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D007511:Ischemia / Q000503:physiopathology*; D007660:Ketoprofen / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D007660:Ketoprofen