Potentiation of Bradykinin by Angiotensin-(1-7) on Resistance Vessels of Hypertensive Rats, Studied in Vivo.
Objective: To verify the Angiotensin-(1-7) [Ang-(1-7)]-activity on Bradykinin (BK)-induced vasodilation in SHR mesenteric arterioles, in vivo-in situ. Methods: Arteriolar diameter was measured by intravital microscopy before and after topical application of BK(1pmol), Acetylcholine(ACh 1.6nmol), Sodium nitroprusside (SNP 38pmol) or Histamine (5.4nmol) in the absence or presence of Ang-(1-7) (100pmol). To investigate the Ang-(1-7)/BK interaction, treatments were employed through topical application of antagonists of BK (HOE140,100pmol), Ang-(1-7)(A779,100pmol)and potassium channel (tetraethylammoniun - TEA,90pmol), with an inhibitor of NOSynthase (L-NAME 10nmol) and after cyclooxygenase blockade (indomethacin 5mg/Kg or diclofenac 2.5mg/Kg). To evaluate the effect of ACE- and/or AT1 blockade on Ang-(1-7)/BK interaction, rats were treated for 21 days with enalapril, quinapril (10mg/Kg), losartan (15mg/Kg) or enalapril + losartan (10 and 15 mg/Kg, respectively). In those enalapril-treated rats the effect of BK (1pmol) was also analysed in the presence of A779 (100pmol). Results: BK-induced vasodilation, but not ACh, SNP or Histamine responses, was increased in the presence of Ang-(1-7) (4.96±0.7% vs 9.07±1.0%*).This interaction was abolished by HOE (1.11±0.8%*), A779 (5.13±0.6%*), TEA (3.37±0.5%*), indomethacin (1.73±0.4%*)and diclofenac (3.63±0.5%*), whereas L-NAME did not modify the Ang-(1-7)-potentiating activity. The BK-potentiation by Ang-(1-7) was also observed after enalapril (10.57±0.5%*), quinapril (8.9±0.7%*), losartan (9.93±1.2%*) and enalapril + losartan (10.59±0.5%*). Enalapril increased the BK-vasodilation(8.21±0.7%*), but this effect was reversed in the presence of A779 (4.27±0.5%*). *p≤0.05 Conclusion: In the SHR microcirculation Ang-(1-7) potentiates BK through a specific receptor, probably releasing prostaglandins and EDHF. Our results indicate that the BK-potentiation by Ang-(1-7) may occur endogenously and contribute to the pharmacological effects of ACE inhibition. HOE 140 and Quinapril were gifts from HOECHST and Warner Lambert, respectively.