Prevention of renal impairment following aortic cross-clamping by manipulation of the endogenous renal nitric oxide response.
OBJECTIVE
Infrarenal aortic cross-clamp-induced lower torso ischaemia-reperfusion injury is associated with impairment of glomerular filtration rate and upregulation of endogenous renal nitric oxide production. The aim of this study was to investigate whether manipulation of the endogenous renal nitric oxide response can ameliorate subsequent renal injury.


METHODS
Groups of male Wistar rats (n = 6) were treated with one of the following agents before being subjected to 60 min of infrarenal aortic cross-clamping: saline (control), L-NMMA (a pan nitric oxide synthase inhibitor), 1400W (a highly selective iNOS inhibitor), hydrocortisone (an inhibitor of the systemic inflammatory response), L-arginine (the substrate for nitric oxide synthase) and NOC-18 (a nitric oxide donor). Animals were recovered after a left nephrectomy. The glomerular filtration rate (GFR) of the remaining kidney was measured on the second and seventh postoperative day using a 99Tc DPTA clearance technique as an index of renal injury.


RESULTS
Animals treated with L-NMMA prior to aortic cross-clamping had a significantly impaired GFR compared to controls on the second (p<0. 01, Mann-Whitney U -test) and seventh (p<0.05, Mann-Whitney U -test) postoperative day. Hydrocortisone and 1400W had no significant effect on GFR on the second or seventh postoperative day. L-arginine and NOC-18 had no influence on GFR on the second postoperative day but significantly improved GFR on the seventh postoperative day.


CONCLUSIONS
These results show that the endogenous nitric oxide response protects the kidneys from ischaemia-reperfusion injury. Manipulation of the renal nitric oxide response may have therapeutic benefits to patients undergoing aortic aneurysm repair by preventing acute renal failure.
Pararajasingam
R
R
Department of Vascular Surgery, Leicester General Hospital, Leicester, UK.
Weight
S C
SC
Bell
P R
PR
Nicholson
M L
ML
Sayers
R D
RD
D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery*; D003250:Constriction; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008297:Male; D009392:Nephrectomy; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D011183:Postoperative Complications / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D011866:Radioisotope Renography / Q000379:methods / Q000706:statistics & numerical data; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D018709:Statistics, Nonparametric; D016284:Technetium Tc 99m Pentetate
D020030:Nitric Oxide Donors; D019275:Radiopharmaceuticals; D009569:Nitric Oxide; D016284:Technetium Tc 99m Pentetate