Gradual reactivation of vascular angiotensin I to angiotensin II conversion during chronic ACE inhibitor therapy in patients with diabetes mellitus

Aims/hypothesis: In chronic heart failure there is gradual reactivation of vascular tissue angiotensin I (AI) to angiotensin II (AII) conversion over time in patients taking chronic ACE inhibitor therapy. However, it remains unknown whether the same overall phenomenon occurs in other patients taking chronic ACE inhibitor therapy, such as patients with type 2 diabetes mellitus. Methods: We studied 30 patients with type 2 diabetes mellitus (mean age 43.5±10.8 years), all of whom received lisinopril (20 mg/day) as part of their normal treatment. Over the course of the 18 month study, we made measurements at 0, 9 and 18 months. These measurements included plasma values for components of the renin-angiotensin-aldosterone system. In addition, we infused AI and AII into the brachial arteries of patients to assess vascular tissue AI to AII conversion. Results: There were no significant changes in plasma renin activity, ACE, AI, AII or aldosterone during the study. In contrast, vascular AI to AII conversion was significantly (p=0.01) greater at 18 months than at 0 months. There was no change over time in the response to infused AII. Conclusions/interpretation: We have shown in vivo that vascular tissue AI to AII conversion gradually increases over time in patients with type 2 diabetes being treated with lisinopril. Further studies are required to determine whether this reactivation detracts from the cardioprotective effects of chronic ACE inhibitor therapy in diabetic patients, and if so, how best to overcome it.