Effects of Losartan on blood pressure, metabolic alterations, and vascular reactivity in the fructose-induced hypertensive rat

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 26; no. 6; pp. 1074 - 1078
• Main Authors: NAVARRO-CID, J, MAESO, R, PEREZ-VIZCAINO, F, CACHOFEIRO, V, RUILOPE, L. M, TAMARGO, J, LAHERA, V
• Format: Conference Proceeding Journal Article
• Language: English
• Published: Philadelphia, PA Lippincott 01.12.1995; Hagerstown, MD American Heart Association, Inc
• Subjects: Analysis of Variance; Angiotensin II - pharmacology; Animals; Antihypertensive agents; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Biological and medical sciences; Biphenyl Compounds - pharmacology; Biphenyl Compounds - therapeutic use; Blood Glucose - analysis; Blood Pressure - drug effects; Cardiovascular system; Endothelins - pharmacology; Fructose; Hypertension - chemically induced; Hypertension - drug therapy; Imidazoles - pharmacology; Imidazoles - therapeutic use; In Vitro Techniques; Insulin - blood; Insulin Resistance; Losartan; Male; Medical sciences; Mesenteric Artery, Superior - drug effects; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Tetrazoles - pharmacology; Tetrazoles - therapeutic use; Triglycerides - blood; Vasoconstriction - drug effects
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.26.6.1074

Fructose feeding induces a moderate increase in blood pressure levels in normal rats that is associated with insulin resistance, hyperinsulinemia, and hypertriglyceridemia. The sympathetic nervous system seems to participate in the alterations of this model. To further explore the mechanisms underlying fructose-induced hypertension, the effects of the AT1 receptor antagonist losartan on blood pressure, insulin resistance, renal function, and vascular reactivity in mesenteric vascular beds were studied. Sprague-Dawley rats were fed for 4 weeks with diets containing 60% fructose or 60% starch (control), and half of each group received losartan (1 mg/kg per day) in the drinking water. Fructose-fed rats showed higher (P < .05) blood pressure levels and plasma concentrations of triglycerides and insulin than those of controls. Losartan treatment prevented both blood pressure elevation and hyperinsulinemia in fructose-fed rats but not elevation of plasma triglycerides. Plasma glucose and insulin levels in response to an oral glucose load were higher (P < .05) in fructose-fed rats than in controls. These exaggerated responses were prevented by losartan treatment. No differences in the constrictor responses of mesenteric vascular beds to KCl (60 mumol), angiotensin II (1 nmol), phenylephrine (10(-5) mol/L), or endothelin-1 (10 pmol) were found between the two groups. Relaxing responses to acetylcholine or sodium nitroprusside in phenylephrine-precontracted mesenteric vascular beds and constrictor response to the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (100 nmol) were comparable in both groups. Losartan blunted angiotensin II constriction and reduced (P < .05) responses to phenylephrine in all groups.