title: The effect of losartan and carvedilol on renal haemodynamics and altered metabolism in fructose-fed Sprague-Dawley rats.
abstract: The aim of this study is to assess the effects of losartan and carvedilol on metabolic parameters and renal haemodynamic responses to angiotensin II (Ang II) and adrenergic agonists in the model of fructose-fed rat. Thirty-six Sprague-Dawley rats were fed for 8 weeks either 20% fructose solution (F) or tap water (C) ad libitum. F or C group received either losartan or carvedilol (10 mg/kg p.o.) daily for the last 3 weeks of the study (FL and L) and (FCV and CV), respectively, then in acute studies the renal vasoconstrictor actions of Ang II, noradrenaline (NA), phenylephrine (PE) and methoxamine (ME) were determined. Data, mean±SEM were analysed using ANOVA with significance at P <0.05. Losartan and carvedilol decreased the area under the glucose tolerance curve of the fructose-fed group. The responses (%) to NA, PE, ME and Ang II in F were lower (P <0.05) than C (F vs. C, 17±2 vs. 38±3; 24±2 vs. 48±2; 12±2 vs. 34±2; 17±2 vs. 26±2), respectively. L had higher (P <0.05) responses to NA and PE while CV had blunted (P <0.05) responses to NA, PE and Ang II compared to C (L, CV vs. C, 47±3, 9±2 vs. 38±3; 61±3, 29±3 vs. 48±2; 16±3, 4±3 vs. 26±2), respectively. FL but not FCV group had enhanced (P <0.05) responses to NA, PE and ME compared to F (FL vs. F, 33±3 vs. 17±2; 45±3 vs. 24±2; 26±3 vs. 12±2), respectively. Losartan and carvedilol had an important ameliorating effect on fructose-induced insulin resistance. Losartan treatment could be an effective tool to restore normal vascular reactivity in the renal circulation of the fructose-fed rat.
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800 Penang, Malaysia, m.abdulla@ucc.ie
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Abdulla
authors.forename: Munavvar A
authors.initials: MA
authors.lastname: Sattar
authors.forename: Nor A
authors.initials: NA
authors.lastname: Abdullah
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Johns
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D005632:Fructose / Q000008:administration & dosage*; D005951:Glucose Tolerance Test; D006439:Hemodynamics; D007333:Insulin Resistance; D007668:Kidney / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D002227:Carbazoles; D011412:Propanolamines; D014662:Vasoconstrictor Agents; D000077261:Carvedilol; D000804:Angiotensin II; D010656:Phenylephrine; D005632:Fructose; D019808:Losartan; D009638:Norepinephrine