Hypoxic pre-conditioning in a rat renal ischemia model: an evaluation of the use of hydralazine.
BACKGROUND
With the advent of improved diagnostic and imaging techniques, it is now possible to detect renal cancers in their very early stages, when they are still present as small renal masses. In these situations, use of laparoscopic partial nephrectomy (LPN) techniques are indicated and have gained acceptance in major medical institutions worldwide, offering comparable oncological outcomes and improving quality of life in the patient when contrasted with open nephrectomy procedures. However, a complication that may occur during or after this surgery is the possibility of compromising renal function, as a result of extended ischemia times of more than 30 min. We have undertaken a systematic study of the potential of several agents that may enhance renal parenchymal preservation without causing unwanted renal dysfunction as a result of enhanced ischemia times. In this study, we have evaluated the potential of one such agent under study, namely hydralazine, which was shown earlier to enhance hypoxia inducible factor-1α (HIF-1α) levels in experimental animal systems. Our aim was to determine whether enhanced levels of HIF-1α via pre-treatment with hydralazine had a reno-protective effect after ischemic injury.


METHODS
Rats were injected with hydralazine or saline for 5 days prior to right nephrectomy and 40 min of cross-clamping of the left renal pedicle. Ischemic damage was monitored via serum chemistry and renal pathology.


RESULTS
In our system, we found that hydralazine pre-treatment, even though it enhanced HIF-1α levels in the kidney, it also increased serum creatinine and worsened the morphological damage to the renal tubules in the ischemic kidney.


CONCLUSIONS
We conclude that even though this agent was described as a powerful inhibitor of prolyl hydroxylases, enhancing the levels of HIF-1α, it should be approached with caution when it is considered to enhance warm ischemia time and minimize the renal damage subsequent to LPN.
Department of Urology, Saint Vincent Medical Center,170 West 12th Street, Cronin-205, New York, NY 10011, USA.
Catherine
C
Michels
Thambi
T
Dorai
Praveen
P
Chander
Muhammad
M
Choudhury
Michael
M
Grasso
D000818:Animals; D001806:Blood Urea Nitrogen; D004195:Disease Models, Animal; D006830:Hydralazine / Q000494:pharmacology*; D000860:Hypoxia / Q000188:drug therapy* / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology; D019194:Ischemic Preconditioning / Q000379:methods*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000473:pathology; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology
C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014665:Vasodilator Agents; D006830:Hydralazine