title: Effects of tempol on altered metabolism and renal vascular responsiveness in fructose-fed rats.
abstract: This study investigated the effect of tempol (a superoxide dismutase mimetic) on renal vasoconstrictor responses to angiotensin II (Ang II) and adrenergic agonists in fructose-fed Sprague-Dawley rats (a model of metabolic syndrome). Rats were fed 20% fructose in drinking water (F) for 8 weeks. One fructose-fed group received tempol (FT) at 1 mmol·L(-1) in drinking water for 8 weeks or as an infusion (1.5 mg·kg(-1)·min(-1)) intrarenally. At the end of the treatment regimen, the renal responses to noradrenaline, phenylephrine, methoxamine, and Ang II were determined. F rats exhibited hyperinsulinemia, hyperuricemia, hypertriglyceridemia, and hypertension. Tempol reduced blood glucose and insulin levels (all p < 0.05) in FT rats compared with their untreated counterparts. The vasoconstriction response to all agonists was lower in F rats than in control rats by about 35%-65% (all p < 0.05). Vasoconstrictor responses to noradrenaline, phenylephrine, and methoxamine but not Ang II were about 41%-75% higher in FT rats compared with F rats (all p < 0.05). Acute tempol infusion blunted responses to noradrenaline, methoxamine, and Ang II in control rats by 32%, 33%, and 62%, while it blunted responses to noradrenaline and Ang II in F rats by 26% and 32%, respectively (all p < 0.05), compared with their untreated counterparts. Superoxide radicals play a crucial role in controlling renal vascular responses to adrenergic agonists in insulin-resistant rats. Chronic but not acute tempol treatment enhances renal vascular responsiveness in fructose-fed rats.
authors.affiliation: a Department of Physiology, School of Medicine, University College Cork, Cork, Ireland.
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Abdulla
authors.affiliation: b School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, 11800 Penang, Malaysia.
authors.forename: Munavvar A
authors.initials: MA
authors.lastname: Sattar
authors.affiliation: a Department of Physiology, School of Medicine, University College Cork, Cork, Ireland.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Johns
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D005632:Fructose / Q000008:administration & dosage; D008297:Male; D008660:Metabolism / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000187:drug effects*; D013113:Spin Labels; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D000322:Adrenergic Agonists; D000975:Antioxidants; D003497:Cyclic N-Oxides; D013113:Spin Labels; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D005632:Fructose; C001803:tempol
keywords: Sprague–Dawley rats; angiotensin II; angiotensine II; fructose; hypertension; rats Sprague-Dawley; tempol