Additive hypotensive and anti-albuminuric effects of angiotensin-converting enzyme inhibition and angiotensin receptor antagonism in diabetic spontaneously hypertensive rats

Angiotensin II plays a pivotal role in the development of diabetic nephropa thy, but it remains controversial as to the best approach to effectively bl ock the actions of this hormone in the kidney. The aim of the present study was to explore the effects of long-term treatment (8 months) with a combin ation of an angiotensin type I (ATI) receptor antagonist, irbesartan (15 mg /kg per day), and an angiotensin-converting enzyme (ACE) inhibitor, captopr il ( 100 mg/kg per day), in diabetic spontaneously hypertensive rats. Capto pril treatment reduced blood pressure (163 +/-3 mmHg versus diabetic 201 +/ -3 mmHg), but not albumin excretion rate (43.8 x /divided by 1.3 mg/day ver sus diabetic 46.8 x / divided by 1.4 mg/day). Irbesartan treatment was asso ciated with a similar reduction in blood pressure 1173 +/-3 mmHg) to captop ril, and albumin excretion rate was reduced (14x /divided by 1.5 mg/day). T he combination of irbesartan and captopril induced further reductions in bl ood pressure (140 +/-3 mmHg) and albumin excretion rates (4.0 x /divided by 1.5 mg/day). Gene expression of transforming growth factor beta- 1 was red uced by all treatments to a similar level as assessed by in situ hybridizat ion. These results demonstrate the additive hypotensive and anti-albuminuri c effects of an ACE inhibitor and an ATI receptor, suggesting that combinat ion therapy is an approach not only more effective at reducing blood pressu re, but also at retarding the development of diabetic nephropathy.