Acute effects of the superoxide dismutase mimetic tempol on split kidney function in two-kidney one-clip hypertensive rats.
OBJECTIVE
To investigate the acute effects of the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol) on split kidney function, and renal haemodynamics, in two-kidney, one-clip (2K1C) hypertensive rats.


METHODS
Three weeks after clipping, or the sham procedure, the effects of intravenous tempol (200 micromol/kg per h) were evaluated on thiobutabarbital anaesthetized Sprague-Dawley rats.


RESULTS
Mean arterial pressure (MAP; 152 +/- 3 versus 122 +/- 3 mmHg, P < 0.001), plasma renin activity (28.7 +/- 3.0 versus 9.5 +/- 0.6 ng/ml per h, P < 0.001) and urinary 8-iso-prostaglandin F2alpha excretion (124 +/- 4 versus 92 +/- 10 pmol/24 h, P = 0.003) were significantly elevated in 2K1C rats compared with sham. Tempol reduced MAP by 15 +/- 1% compared with baseline (P < 0.001) in 2K1C rats. In clipped kidneys, tempol increased the glomerular filtration rate (GFR; +50 +/- 15% from baseline) and the effective renal plasma flow (ERPF; +37 +/- 13%, from baseline), and reduced renal vascular resistance (RVR; -32 +/- 6% from baseline) compared with saline-treated controls (P < 0.05). In non-clipped kidneys, tempol reduced RVR (-24 +/- 5% from baseline) compared with saline-treated controls (P = 0.001). In sham-operated rats, tempol produced a modest reduction in MAP (-8 +/- 2% from baseline, P = 0.003), but did not significantly affect renal haemodynamics or function.


CONCLUSIONS
Tempol reduced MAP and RVR in both clipped and non-clipped kidneys of 2K1C hypertensive rats. In addition, tempol increased ERPF and GFR in the clipped kidney. These findings suggest important roles for superoxide in the regulation of renal haemodynamics during the early maintenance phase of renovascular hypertension.
Guron
Gregor S
GS
Department of Nephrology, Institute of Internal Medicine, Göteborg, Sweden. Gregor.Guron@kidney.med.gu.se
Grimberg
Elisabeth S
ES
Basu
Samar
S
Herlitz
Hans
H
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017596:Renal Plasma Flow, Effective / Q000187:drug effects; D012083:Renin / Q000097:blood; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects
D003497:Cyclic N-Oxides; D013113:Spin Labels; D013481:Superoxides; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D015237:Dinoprost; D012083:Renin; D009543:Nifedipine; C001803:tempol