Aims: 

The goal of our study was to analyse a time course of L-NAME effects on eNOS, nNOS and iNOS protein expressions, NOS activity, membrane oxidative damage and blood pressure (BP), respectively.

Methods: 

Adult 12-week-old male Wistar rats were divided into three groups: control, L-NAME (40 mg/kg/day) for four weeks and L-NAME (40 mg/kg/day) for seven weeks.

Results: 

Both 4- and 7-week-L-NAME treatments increased BP in comparison with controls. After 4 weeks of L-NAME treatment eNOS expression in the heart increased significantly and this increase was amplified after 7 weeks of treatment. On the other hand, eNOS expression in the brain remained unchanged after 4-week-L-NAME treatment and prolonging the treatment led to significant decrease of eNOS expression in this tissue. There were no changes in protein expressions of other isoforms. NOS activity was decreased after 4 weeks of L-NAME treatment in both tissues. However, prolonging the treatment to 7 weeks increased NOS activity in the heart while NOS activity in the brain was decreased more significantly. Oxidative damage was detected in both tissues after 4-week-L-NAME treatment. Prolonging the treatment amplified the damage in the brain only.

Conclusion: 

Increased expression of eNOS may be responsible for increased NOS activity and reduced oxidative damage in the heart after 7-week-L-NAME treatment. Decreased expression of eNOS led, however, to more significant decrease of NOS activity and oxidative damage in the brain. Since BP increase persisted after 7 weeks of L-NAME treatment, we hypothesised that central regulation of BP is predominant in L-NAME-induced hypertension.