Enalapril improves vascular and cardiac function in streptozotocin-diabetic rats

Recent evidence points to the renin-angiotensin system (RAS) as one of the systems involved in the etiology of micro- and macrovascular disease in diabetic patients. To help elucidate this possibility, the effect of daily treatment with enalapril (25 mg/kg/d) was evaluated in streptozotocin (STZ)-diabetic rats at 2 weeks following the induction of diabetes. Untreated diabetic rats and non-diabetic rats that were age-matched were used for comparison. Vascular studies included the determination of aortic ring responses to norepinephrine (NE), angiotensin II (Ang II) and acetylcholine (Ach). Systolic blood pressure (SBP), cardiac output (CO) indices, plasmatic and vascular angiotensin-converting enzyme (ACE) activity and thickness of the aortic wall were also assessed. Enalapril improved Ach-induced relaxation by increasing the maximal relaxation from 54.3 +/- 4.3% in untreated diabetic rats to 89.8 +/- 6.2% (n=9, p<0.05) and by decreasing the EC50 value from 32.6 +/- 9.9 nmol/l in untreated diabetic animals to 17.9 +/- 5.1 nmol/l (n=8, p<0.05). In addition, enalapril normalized the high responses to NE found in diabetic rats without inducing changes in the EC50 value. A significant reduction in SBP (from 158 +/- 4 mm Hg to 123 +/- 1 mm Hg, p<0.05), combined with an improved CO index (from 40 +/- 2 ml/min x 100 g BW to 50 +/- 1 ml/min x 100 g BW), was observed in the enalapril-treated diabetic group. A significant regression of the media thickness was also observed in the aorta of diabetic rats after treatment. ACE activity in the aorta of diabetic rats, that was doubled compared to controls (p<0.05), decreased after enalapril treatment. These results point to the vascular RAS as one of the key systems in the etiology of vascular alterations at early stages of diabetes. Therefore, ACE inhibitors, as well as other pharmacological approaches targeting the vascular RAS, should be considered in the treatment of diabetic patients from the very early stages of the condition.