Allopurinol and enalapril failed to conserve urinary NOx and sodium in ischemic acute renal failure in spontaneously hypertensive rats.
BACKGROUND
Ischemia-reperfusion-induced acute renal failure (ARF) is associated with a high mortality in patients with hypertension and with an unfavorable outcome of kidney transplants from marginal donors.


OBJECTIVE
The influence of allopurinol and enalapril on urinary nitrate/nitrite (UNOx), glomerular filtration rate, plasma and urinary sodium, and hemodynamic parameters was examined in spontaneously hypertensive rats (SHR) with ARF.


METHODS
ARF was induced by right-kidney removal and clamping the left renal artery for 40 min in 50 male 26-week-old SHR weighing 300 +/- 23 g. The rats were randomly allocated to five groups: (1) sham operated; (2) ARF; (3) ARF after pretreatment with 40 mg/kg allopurinol; (4) ARF after pretreatment with 40 mg/kg enalapril, and (5) ARF after pretreatment with 40 mg/kg allopurinol and 40 mg/kg enalapril. Creatinine clearance, UNOx (Griess reaction), cardiac output (dye dilution technique), mean arterial blood pressure, and renal blood flow were measured 24 h after reperfusion. Total vascular resistance and renal vascular resistance were calculated and compared between the groups.


RESULTS
A nonsignificant decrease was found in both daily UNOx excretion and creatinine clearance when pretreated ARF groups and the ARF group without pretreatment were compared (p > 0.05). Significantly lower plasma sodium values (139.5 +/- 4.86 mmol/l) in the allopurinol-pretreated ARF group were found than in the ARF group without pretreatment, in the ARF group pretreated with enalapril, and in the sham SHR group (p = 0.029). The urinary sodium loss was greater in the enalapril-pretreated than in the allopurinol-pretreated ARF group (p = 0.047). Allopurinol and/or enalapril pretreatment decreased total vascular resistance (p = 0.003) in comparison with the sham SHR group.


CONCLUSIONS
Neither allopurinol nor enalapril nor both were protective against ischemia-reperfusion injury in SHR, nor altered glomerular filtration rate and UNOx in a favorable direction.
Radovic
Milan
M
Institute for Medical Research, Belgrade, Serbia. milan.r@EUnet.yu
Miloradovic
Zoran
Z
Popovic
Tamara
T
Mihailovic-Stanojevic
Nevena
N
Jovovic
Djurdjica
D
Tomovic
Mina
M
Colak
Emina
E
Simic-Ogrizovic
Sanja
S
Djukanovic
Ljubica
L
D058186:Acute Kidney Injury / Q000209:etiology / Q000517:prevention & control / Q000652:urine*; D000493:Allopurinol / Q000008:administration & dosage*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D000963:Antimetabolites / Q000008:administration & dosage; D004338:Drug Combinations; D004656:Enalapril / Q000008:administration & dosage*; D008297:Male; D009566:Nitrates / Q000652:urine*; D009573:Nitrites / Q000652:urine*; D051381:Rats; D011918:Rats, Inbred SHR; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism* / Q000517:prevention & control; D012964:Sodium / Q000652:urine*; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D000963:Antimetabolites; D004338:Drug Combinations; D009566:Nitrates; D009573:Nitrites; D000493:Allopurinol; D004656:Enalapril; D012964:Sodium