LISINOPRIL IMPROVES ENDOTHELIAL DYSFUNCTION IN HYPERTENSIVE NIDDM SUBJECTS WITH DIABETIC NEPHROPATHY

Endothelial dysfunction is a prevalent phenomenon in non-insulin depen dent diabetic (NIDDM) patients with hypertension and albuminuria, and may contribute to the development and progression of cardiovascular di sease, which is the main cause of the high morbidity and mortality obs erved in these patients. Therefore the aim of our study was to evaluat e 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. W e 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 variable s were measured: 24-h ambulatory blood pressure (ABP); transcapillary escape rate of albumin (TERalb; i.e. initial disappearance of intraven ously injected I-125-labelled human serum albumin); serum concentratio ns of von Willebrand factor (vWF), using ELISA, and urinary albumin ex cretion 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 TERalb. At baseline the two g roups were comparable: TERalb (8.5 (SEM 0.6) vs. 7.2(0.4) %); vWF (2.0 9 (range 0.82-4.34) vs. 1.97 (0.95-3.86) IU ml(-1); UAE 916 (x/divided by 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 f ollow up, the mean ABP was equally reduced in the lisinopril and ateno lol group, by 12 (SEM 2) vs. 10 (2) mmHg, respectively. TERalb decreas ed 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 th e 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 stud y suggests that lisinopril has both reno-and vasculoprotective propert ies in hypertensive NIDDM patients with diabetic nephropathy.