Superoxide and its interaction with nitric oxide modulates renal function in prehypertensive Ren-2 transgenic rats.
OBJECTIVE
The present study was performed to examine the role of superoxide (O2*) and its interaction with nitric oxide (NO) in the regulation of renal function in prehypertensive heterozygous Ren-2 transgenic rats (TGR).


METHODS
Renal responses to the O2* scavenger, tempol (150 microg/min per 100 g), and/or the NO synthase inhibitor, nitro-L-arginine methylester (L-NAME; 5 microg/min per 100 g), infused alone or in combination directly into the renal artery were evaluated in anesthetized heterozygous male TGR and aged-matched Hanover Sprague-Dawley rats (HanSD).


RESULTS
There were no differences in arterial pressure (122 +/- 3 versus 115 +/- 2 mmHg), renal plasma flow (RPF; 2.09 +/- 0.1 versus 2.07 +/- 0.1 ml/min per g), glomerular filtration rate (GFR; 0.73 +/- 0.1 versus 0.74 +/- 0.1 ml/min per g) or sodium excretion (0.63 +/- 0.13 versus 0.67 +/- 0.16 micromol/min per g) between TGR and HanSD. Tempol alone caused significant increases in RPF and GFR (10 +/- 4% and 12 +/- 2%, respectively) in TGR but not in HanSD. Tempol also caused greater sodium excretory responses in TGR compared to HanSD (112 +/- 16% versus 43 +/- 7%; P < 0.05). 8-Isoprostane excretion was significantly higher in TGR than in HanSD (10.2 +/- 0.8 versus 6.5 +/- 0.7 pg/min per g), which was attenuated by tempol. L-NAME caused greater decreases in RPF and GFR in TGR (-34 +/- 4% and -22 +/- 4%, respectively) than in HanSD (-19 +/- 3% and -10 +/- 4%, respectively). Co-infusion of tempol partially attenuated the renal hemodynamic and excretory responses to L-NAME in TGR.


CONCLUSIONS
These data suggest that the enhanced O2* activity and its interaction with NO during the prehypertensive phase in TGR modulates renal hemodynamic and excretory function, which may contribute to the development of hypertension in this transgenic rat model.
Kopkan
Libor
L
Department of Physiology, Tulane Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, Louisianna, USA. likp@medicon.cz
Husková
Zuzana
Z
Vanourková
Zdenka
Z
Thumová
Monika
M
Skaroupková
Petra
P
Cervenka
Ludek
L
Majid
Dewan S A
DS
D000818:Animals; D030801:Animals, Genetically Modified; D001794:Blood Pressure; D003497:Cyclic N-Oxides / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D007668:Kidney / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000235:genetics*; D012964:Sodium / Q000652:urine; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism*
D003497:Cyclic N-Oxides; D013113:Spin Labels; D013481:Superoxides; D009569:Nitric Oxide; D012964:Sodium; D012083:Renin; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester