title: High-fructose feeding impacts on the adrenergic control of renal haemodynamics in the rat.
abstract: The present study explored the hypothesis that a prolonged 8 weeks exposure to a high fructose intake suppresses adrenergic and angiotensin II (Ang II)-mediated vasoconstriction and is associated with a higher contribution of α1D-adrenoceptors. A total of thirty-two Sprague-Dawley rats received either 20 % fructose solution (FFR) or tap water (control, C) to drink ad libitum for 8 weeks. Metabolic and haemodynamic parameters were assessed weekly. The renal cortical vasoconstrictor responses to noradrenaline (NA), phenylephrine (PE), methoxamine (ME) and Ang II were determined in the presence and absence of BMY7378 (α1D-adrenoceptor antagonist). FFR had increased blood pressure, plasma levels of glucose, TAG and insulin. FFR expressed reduced renal vascular responses to adrenergic agonists and Ang II (NA: 50 %, PE: 50 %, ME, 65 %, Ang II: 54 %). Furthermore in the C group, the magnitude of the renal cortical vasoconstriction to all agonists was blunted in the presence of the low or high dose of BMY7378 (NA: 30 and 31 %, PE: 23 and 33 %, ME: 19 and 44 %, Ang II: 53 and 77 %), respectively, while in the FFR, vasoconstriction was enhanced to adrenergic agonists and reduced to Ang II (NA: 8 and 83 %, PE: 55 %, ME, 2 and 177 %, Ang II: 61 and 31 %). Chronic high fructose intake blunts vascular sensitivity to adrenergic agonists and Ang II. Moreover, blocking of the α1D-adrenoceptor subtype results in enhancement of renal vasoconstriction to adrenergic agonists, suggesting an inhibitory action of α1D-adrenoceptors in the FFR. α1D-Adrenoceptors buffer the AT1-receptor response in the renal vasculature of normal rats and fructose feeding suppressed this interaction.
authors: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, 11800 Penang, Malaysia. mdapharm78@yahoo.co.uk
authors: Mohammed H
authors: MH
authors: Abdulla
authors: Munavvar A
authors: MA
authors: Sattar
authors: Edward J
authors: EJ
authors: Johns
authors: Nor A
authors: NA
authors: Abdullah
authors: Md Abdul
authors: MA
authors: Hye Khan
authors: Hassaan A
authors: HA
authors: Rathore
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000009:adverse effects*; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects*; D006439:Hemodynamics / Q000187:drug effects; D006943:Hyperglycemia / Q000097:blood / Q000209:etiology; D006946:Hyperinsulinism / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism; D015228:Hypertriglyceridemia / Q000097:blood / Q000209:etiology; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000737:chemistry / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000737:chemistry / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: C547721:Adra1d protein, rat; D058646:Adrenergic alpha-1 Receptor Agonists; D000317:Adrenergic alpha-Antagonists; C524087:Agtrap protein, rat; D004040:Dietary Carbohydrates; D018340:Receptors, Adrenergic, alpha-1; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D005632:Fructose; D009638:Norepinephrine