Background: 

The kidneys play a key role in the homeostatic regulation of body fluid status, and an impaired renal function has been demonstrated in salt-sensitive hypertension. During the last years it has become evident that NO systems play an important role in blood pressure regulation and that NO deficiency may in fact be involved in the development of hypertension. To investigate the mechanisms for this worldwide growing disorder we have used different experimental models: 1) Chronic blockade of nNOS in rats 2) Hydronephrosis induced by chronic partial ureteral obstruction 3) Reduction in nephron number after completed nephrogenesis 4) Genetic modified mice (nNOS-deficient, SOD1- deficient, SOD1-transgenic)

Methods: 

Renal function in terms of blood flow, glomerular filtration rate, electrolyte excretion has been investigated. The tubuloglomerular feedback (TGF) mechanism was investigated by stop-flow pressure technique. Blood pressure and heart rate was measured both acutely and with telemetry, during different sodium conditions (i.e. low, normal and high NaCl-diet). Renal microcirculation was investigated by studying the responsiveness in isolated and perfused afferent arterioles of mice.

Results: 

In our models, we have found that reduced renal NO availability and subsequent resetting of the TGF-response plays an important role for the development of salt-sensitive hypertension. Oxidative stress (by superoxide) can enhance the TGF responsiveness, both directly by constricting afferent arterioles and indirectly by scavenging NO, and thereby play an important role in the development and maintenance of hypertension. Treatment modalities that increase NO or decrease oxidative stress can attenuate the salt- sensitive hypertension. In this presentation the results of our studies will be discussed.