Lisinopril improves endothelial dysfunction in hypertensive NIDDM subjects with diabetic nephropathy

Abstract

Endothelial dysfunction is a prevalent phenomenon in non-insulin dependent diabetic (NIDDM) patients with hypertension and albuminuria, and may contribute to the development and progression of cardiovascular disease, which is the main cause of the high morbidity and mortality observed in these patients. Therefore the aim of our study was to evaluate whether inhibition of angiotensin-converting enzyme (with lisinopril 10-20 mg day^-1) could ameliorate endothelial dysfunction more than reducing blood pressure with conventional antihypertensive treatment (atenolol 50-100 mg day^-1), usually in combination with a diuretic. We performed a 12-month prospective, randomized, double-blind, parallel study in 43 hypertensive NIDDM patients with diabetic nephropathy (21 treated with lisinopril and 22 with atenolol). The following variables were measured: 24-h ambulatory blood pressure (ABP); transcapillary escape rate of albumin (TER_alb; i.e. initial disappearance of intravenously injected ¹²⁵I-labelled human serum albumin); serum concentrations of von Willebrand factor (vWF), using ELISA, and urinary albumin excretion rate (UAE). Data are presented for 32 patients (16 lisinopril and 16 atenolol; age 60 years, SD 8; 25 males) out of 35 who completed the study and had valid measurements of TER_alb. At baseline the two groups were comparable: TER_alb (8.5 (SEM 0.6) vs. 7.2 (0.4) %); vWF (2.09 (range 0.82–4.34) vs. 1.97 (0.95–3.86) IU ml^-1; UAE 916 (x/÷ antilog SEM 1.3) vs. 1444 (1.2), and mean ABP 110 (SEM 3) vs. 113 (2) mmHg, in the lisinopril and atenolol group, respectively. During follow up, the mean ABP was equally reduced in the lisinopril and atenolol group, by 12 (SEM 2) vs. 10 (2) mmHg, respectively. TER_alb decreased in the lisinopril group by 0.6 (SEM 0.7) %, whereas it increased in the atenolol group 1.5 (0.5) %; the mean difference was 2.2% (95% CI, 0.5 to 3.9; p=0.015). UAE was reduced by 45% (95% CI, 25 to 60) in the lisinopril group vs. 10% (-15 to 30) in the atenolol group (p=0.014). Serum vWF was not changed during follow up in either group. Our study suggests that lisinopril has both reno- and vasculo-protective properties in hypertensive NIDDM patients with diabetic nephropathy.

Key Words:

• antihypertensive treatment
• arterial hypertension
• cardiovascular disease
• transcapillary escape rate of albumin
• urinary albumin excretion rat
• von Willebrand factor