Plasma endothelin-1 immunoreactivity is increased following long-term dietary supplementation withΩ-3 fatty acids in microalbuminuric IDDM patients

✍ Scribed by P. L. Selvais

• Publisher: Springer
• Year: 1995
• Tongue: English
• Weight: 113 KB
• Volume: 38
• Category: Article
• ISSN: 0012-186X
• DOI: 10.1007/bf00400104

✦ Synopsis

Dear Sir, Circulatory concentrations of plasma endothelin-1 (ET-1), an endogenous vasoactive peptide, are increased in diabetes mellitus. Raised ET-1 levels have been proposed as a marker of endothelial dysfunction in this disease [1,2]. We hypothesize that ET-1 changes could be associated with the endothelial/rheological effects of supplements of c0-3 fatty acids (o-3 FAs), a dietary intervention advocated in diabetes [3].

We measured plasma ET-1 immunoreactivity in 18 microalbuminuric IDDM patients (urinary albumin excretion rate 30-300 mg/24 h in at least two of three consecutive urinary collections), who were treated for 9 months, according to a double-blind schedule, with either 2.4 g/day co -3 FAs (84 % eicosapentaenoic, 16 % docosahexaenoic acids; gift of Sanofi, Brussels, Belgium; n = 8) or an inert placebo (n = 10). Patients in the two groups were comparable for age, sex, duration and complications of diabetes, insulin requirements, HbAlc , body mass index and waist-hip ratio. We also measured plasma ET-1 in a group of normoalbuminuric IDDM patients (n = 23) as control. Plasma was obtained from venous blood taken into 9 mmol/1 benzamidine and 3 mmol/1 EDTA, and stored at -80~

ET-1 immunoreactivity was measured as previously described [4], after extraction on Cls-Se p Pack (Millipore, Milford, Mass., USA), using commercial antibody and standard (Peninsula Labs, Belmont, Calif., USA).

As previously reported [5], ET-1 immunoreactivity was higher in microalbuminuric than in normoalbuminuric patients (1.9 + 0.2 vs 1.5 + 0.2 pmol/1, mean • SEM, n = 10 and 23, p < 0.05, Mann-Whitney's test). ET-1 immunoreactivity was further increased in co -3 FAs-supplemented microalbuminuric diabetic patients compared with those receiving placebo (2.4 + 0.1 vs 1.9 _+ 0.2 pmol/1, mean +_ SEM, n = 8 and 10, p < 0.05). ET-1 immunoreactivity was further characterized in one non-microalbuminuric, two placebo-treated microalbuminuric, and three co -3 FAs-supplemented microalbuminuric diabetic patients by reverse phase HPLC (24-44% acetonitrile gradient on a CIsTSKODS-120 T column, Toso Haas, Germany) (Fig. 1). ET-1 immunoreactivity elute d similarly to synthetic ET-1 (Peninsula), appearing as two peaks, corresponding to oxidized-ET-1 and to the intact peptide (ET-1). Weak immunoreactivity was also detected close to the elution position of synthetic big ET-1. In contrast to ET-1, the immunoreactivity of plasma angiotensin II, another vasoconstrictor peptide, was similar in co-3 FAsand piacebo-supplemented patients (12.6 + 1.8 vs 14.6 + 1.9 pmol/1, n = 8 and 10).

In conclusion, ET-1 plasma immunoreactivity is increased following long-term dietary supplementation with co-3 FAs to