title: Neutral endopeptidase inhibitor versus angiotensin converting enzyme inhibitor in a rat model of the metabolic syndrome.
abstract: 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.
authors.affiliation: Institute of Endocrinology and Metabolism, Beilinson Campus, Rabin Medical Center, Petach Tikva 49100, Israel; Affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address: yoave1@yahoo.com.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Eizenberg
authors.affiliation: Hypertension Unit, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel; Affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Ehud
authors.initials: E
authors.lastname: Grossman
authors.affiliation: Hypertension Unit, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel; Affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Edna
authors.initials: E
authors.lastname: Peleg
authors.affiliation: Hypertension Unit, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
authors.forename: Zehava
authors.initials: Z
authors.lastname: Shabtai
authors.affiliation: Hypertension Unit, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel; Affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Yehonatan
authors.initials: Y
authors.lastname: Sharabi
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004656:Enalapril / Q000494:pharmacology*; D007189:Indans / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007189:Indans; D007328:Insulin; D011422:Propionates; D014280:Triglycerides; D004656:Enalapril; C062766:candoxatril
keywords: Candoxatril; atrial natriuretic peptide; enalapril