1. Enhanced
superoxide (O2(-)) activity as a result of the inhibition of the
superoxide dismutase (SOD)
enzyme results in
vasoconstrictor and antinatriuretic responses in the canine kidney; these responses were shown to be greatly enhanced during inhibition of
nitric oxide synthase (NOS). Glomerular filtration rate remained mostly unchanged during SOD inhibition in the intact
nitric oxide (NO) condition, but was markedly reduced during NOS inhibition. These findings indicate that endogenous NO has a major renoprotective effect against O2(-) by acting as an
anti-oxidant.
Nitric oxide synthase inhibition was also shown to enhance endogenous O2(-) activity. 2. Experiments in our laboratory using dogs, rats and gene knockout mice have shown that renal
vasoconstrictor and antinatriuretic responses to acute or chronic
angiotensin (Ang) II administration are mediated, in part, by O2(-) generation. In the absence of NO, enhanced O2(-) activity largely contributes to AngII-induced renal tubular
sodium reabsorption. Acute or chronic treatment with the O2(-) scavenger
tempol in experimental models of
hypertension (induced by chronic low-dose treatment with AngII and NO inhibitors) causes an improvement in renal haemodynamics and in excretory function, abolishes
salt sensitivity and reduces blood pressure. 3. The present mini review also discusses related studies from many other laboratories implicating a role for O2(-) and its interaction with NO in the development of
salt-sensitive
hypertension. 4. Overall, the collective data support the hypothesis that an imbalance between the production of NO and O2(-) in the kidney primarily determines the condition of oxidative stress that alters renal haemodynamics and excretory function leading to
sodium retention and, thus, contributes to the development of
salt-sensitive
hypertension.