Antihypertensive treatment with enrasentan (SB217242) in an animal model of hypertension and hyperinsulinemia.
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.
Cosenzi
Alessandro
A
Dipartimento di Medicina Clinica e Neurologia, Ospedale di Cattinara, Università di Trieste, Strada di Fiume, 31400 Trieste, Italy. a.cosenzi@fmc.units.it
Bernobich
E
E
Bonavita
M
M
Bertola
G
G
Trevisan
R
R
Bellini
G
G
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
D002264:Carboxylic Acids; D004040:Dietary Carbohydrates; D065128:Endothelin Receptor Antagonists; D007189:Indans; D005632:Fructose; D003094:Collagen; C098288:enrasentan