Antioxidant enzymes and effects of tempol on the development of hypertension induced by nitric oxide inhibition.
BACKGROUND
This study analyzed whether hypertension induced by N(omega)-nitro-l-arginine methyl ester (L-NAME) is associated with dysregulation of the main antioxidant enzymes (superoxide dismutase [SOD], catalase, glutathione peroxidase [GPX], and glutathione reductase [GR]) and whether chronic administration of tempol ameliorates this hypertension.


METHODS
Four groups of male Wistar rats were used: 1) control rats; 2) rats treated with L-NAME (35 mg/100 mL in drinking fluid); 3) rats treated with tempol (18 mg/100 mL in drinking fluid); and 4) rats treated with L-NAME plus tempol. All treatments were maintained for 6 weeks. Body weight, systolic blood pressure (BP) determined by the tail-cuff method, and heart rate were measured once per week. At the end of the experimental period, direct BP and morphologic, metabolic, plasma, and renal variables were measured. Enzymatic activities were measured in the kidney (cortex and medulla) and heart (right and left ventricles).


RESULTS
Rats with L-NAME-induced hypertension showed increased copper-zinc (Cu-Zn) SOD activity in the renal cortex and medulla and the left and right ventricles, which was reduced by tempol administration. The manganese (Mn) SOD activity was increased by L-NAME and reduced by tempol in the renal cortex but was unchanged in other tissues. Catalase activity was not affected by L-NAME or tempol treatments in any tissue. Both GPX and GR activities were increased by L-NAME and reduced by tempol in the renal cortex and medulla but were not affected in the ventricles. Tempol reduced BP and total urinary excretion of 8-hydroxy-2'-deoxyguanosine in L-NAME-treated animals but did not affect either variable in controls.


CONCLUSIONS
We conclude that L-NAME-induced hypertension is associated with an upregulation of antioxidant SOD, GPX, and GR activities. Moreover, the results indicate that tempol attenuates hypertension on nitric oxide-deficient rats and that oxidative stress participates in the established phase of this type of hypertension.
Sainz
Juan
J
Departamento de Fisiología, Facultad de Medicina, Granada, Spain.
Wangensteen
Rosemary
R
Rodríguez Gómez
Isabel
I
Moreno
Juan Manuel
JM
Chamorro
Virginia
V
Osuna
Antonio
A
Bueno
Pablo
P
Vargas
Félix
F
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D005980:Glutathione Reductase / Q000187:drug effects / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000201:enzymology / Q000473:pathology; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D007672:Kidney Cortex / Q000201:enzymology / Q000473:pathology; D007679:Kidney Medulla / Q000201:enzymology / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013053:Spectrophotometry; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D015415:Biomarkers; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D013113:Spin Labels; D009569:Nitric Oxide; D000080242:8-Hydroxy-2'-Deoxyguanosine; D010088:Oxidoreductases; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D003849:Deoxyguanosine; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester