The renin-angiotensin system in type 1 diabetes mellitus: renal hemodynamic responses to captopril and candesartan

Enhanced renal vasodilator responses to ACE inhibition (ACEI) in diabetes mellitus (DM) despite a normal or low plasma renin activity level have suggested intrarenal activation of the renin-angiotensin system (RAS) in this disease. There is, however, a continuing debate as to the mediators of the renal hemodynamic response to the mediators of the renal hemodynamic response to ACEI—angiotensin II or pathways involving kinins, prostaglandins and nitric oxide. Twelve patients with type 1 DM (7 females, 5 males, ages 17 to 50, mean ± SEM, 32 ± 4.0 years) on a high salt diet were given captopril 25 mg p.o. on one day and candesartan 16 mg p.o. on the next. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured before and for 4 hours after administration. Both drugs caused a significant increase in RPF (Captopril 574 ± 26 to 625 ± 37 mL/min/1.73 m2, p = 0.008; candesartan 577 ± 26 to 643 ± 37, p = 0.004). There was a highly significant correlation between the responses to captopril and to candesartan (r = 0.86, p < 0.001), and these were not statistically different (p = 0.13). There was no significant change in GFR on either drug. The rise in RPF on either captopril or candesartan despite high sodium balance supports the intrarenal activation of the RAS in diabetic subjects not reflected in plasma levels. The remarkable correlation between the renal hemodynamic responses to captopril and to candesartan indicates that AngII blockade is the main mechanism of action of ACE inhibitors.