title: Antihypertensive treatment with enrasentan (SB217242) in an animal model of hypertension and hyperinsulinemia.
abstract: Enrasentan is an antagonist of endothelin (ET) receptors. Previous studies have shown that antagonism of ET receptors might represent a new approach to the treatment of hypertension. Rats with a high-fructose diet (HFD) develop hyperinsulinemia, hypertriglyceridemia, and hypertension; renal and cardiac damage. The aim of this study was to evaluate whether enrasentan could reverse the hypertension and reduce the target organ damage induced by an HFD. Fifty-five WKY rats were divided into 6 groups; 35 animals received HFD for a month; thereafter 5 animals were killed, and the others were treated either with enrasentan (n = 10), hydralazine (n = 10), or placebo (n = 10) for a further month while on the HFD. Twenty animals were kept on a standard diet throughout the study; either placebo (n = 10) or enrasentan (n = 10) was administered during the second month. Enrasentan and hydralazine completely eliminated the HFD-induced increase in blood pressure; however, only enrasentan reduced the renal and cardiac damage caused by the diet. In conclusion, enrasentan was effective both in normalizing blood pressure and in reducing renal and cardiac damage; the organ protection cannot be attributed solely to the antihypertensive effect, because it was absent in the case of hydralazine, despite successful control of blood pressure.
authors.affiliation: Dipartimento di Medicina Clinica e Neurologia, Ospedale di Cattinara, Università di Trieste, Strada di Fiume, 31400 Trieste, Italy. a.cosenzi@fmc.units.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cosenzi
authors.forename: E
authors.initials: E
authors.lastname: Bernobich
authors.forename: M
authors.initials: M
authors.lastname: Bonavita
authors.forename: G
authors.initials: G
authors.lastname: Bertola
authors.forename: R
authors.initials: R
authors.lastname: Trevisan
authors.forename: G
authors.initials: G
authors.lastname: Bellini
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002264:Carboxylic Acids / Q000627:therapeutic use*; D003094:Collagen / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004195:Disease Models, Animal; D065128:Endothelin Receptor Antagonists; D005632:Fructose / Q000008:administration & dosage; D006946:Hyperinsulinism / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007189:Indans / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011921:Rats, Inbred WKY
chemical_list: D002264:Carboxylic Acids; D004040:Dietary Carbohydrates; D065128:Endothelin Receptor Antagonists; D007189:Indans; D005632:Fructose; D003094:Collagen; C098288:enrasentan