Neutral endopeptidase inhibitor versus angiotensin converting enzyme inhibitor in a rat model of the metabolic syndrome

The antihypertensive treatment in patients with metabolic syndrome is unclear. We therefore used a rat model of the metabolic syndrome and compared the effects of enalapril, an angiotensin-converting-enzyme inhibitor, with candoxatril, a neutral endopeptidase inhibitor that inhibits degradation of atrial natriuretic peptide and, in addition to lowering blood pressure, exerts metabolically beneficial activity. Ten male Sprague Dawley rats were fed regular rat chow for 5 weeks. Fifty male Sprague Dawley rats were fed a high-fructose diet for 3 weeks, followed by addition of enalapril, 10 mg/Kg/d, or candoxatril, 25, 50, or 100 mg/Kg/d, for 2 weeks. Systolic blood pressure, plasma triglyceride level, and insulin level were measured at baseline and after 3 weeks and 5 weeks. Three weeks of a high-fructose diet led to a significant increase in all metabolic parameters. Candoxatril and enalapril lowered systolic blood pressure significantly (candoxatril −10 ± 1 to −22 ± 1 mm Hg and enalapril −27 ± 2 mm Hg). High-dose candoxatril and enalapril significantly decreased plasma triglyceride levels (by 17.8% and 32.8%, respectively), but only high-dose candoxatril decreased plasma insulin levels significantly (by 25.3%). High-dose candoxatril is a metabolically favorable option for lowering blood pressure in a rat model of metabolic syndrome.