Objectives: 

In the renin-angiotensin system (RAS), angiotensin-I (Ang-I) is mainly metabolized to angiotensin-II by the enzymatic action of angiotensin-converting enzyme, but Ang-I is also metabolized to des-aspartate-angiotensin-I (DAA-I or Ang2-10) by aspartate or glutamate aminopeptidase activity (APA). The functional role of this peptide is unknown. The present study investigated the effects of DAA-I on vascular reactivity and pressor responses in isolated perfused kidneys, aorta rings and whole rat vascular bed. We also investigated the effects of losartan, an AT1-receptor blocker over DAA-I responses.

Materials: 

All experiments were performed in male Wistar rats in the absence or presence of losartan (n=6 each group). In experiment 1, dose-response curves of DAA-I (0.01-2 mg/kg) were performed in whole rat vascular bed. 10 mg/kg of losartan or saline were injected 30 minutes before the performing of the curve. Experiment 2: DAA-I (10-9-10-6 M) was injected to isolated perfused kidneys. Losartan was added at a concentration of 10-6 M. Experiment 3: DAA-I concentration-response curves (10-9–10-5 M) were performed in aorta rings. Losartan was added at a concentration of 10-6 M.

Results: 

DAA-I produced a dose-related increase on vasoconstrictor and pressor responses in experimental preparations. Losartan reduced the maximal response to DAA-I in isolated kidneys (from 122.9±9.7 to 5±0.5** mmHg) and aorta rings (from 15.7±2.1 to 1.5±0.3**% of KCl 80 mM), and also significantly decreased the maximal response of DAA-I (from 76.7±6.3 to 30.4±9.5* mmHg) in whole rat vascular bed. *p<0.01, **p<0.001 versus control group.

Conclusions: 

DAA-I evokes vasoconstrictor or pressor responses in isolated perfused kidneys, aorta rings and whole rat vascular bed through AT1 receptor activation. Therefore, DAA-I actions might contribute to homeostatic control of arterial pressure and pathogenesis of hypertension and it could be a therapeutic target in the treatment of cardiovascular diseases.