Investigation of basal endothelial function in the obese Zucker rat in vitro.
(a) We studied basal endothelial function in the insulin-resistant, obese Zucker rat, including the influence of superoxide anion on the regulation of contractile reactivity by nitric oxide (NO), following treatment in vivo with the antioxidant tiron or the pro-oxidant combination hydroquinone+buthionine sulfoximine. (b) The leftward shift in the contractile potency of phenylephrine due to NO synthase inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) was greater in the isolated aorta of the obese Zucker rat relative to its insulin-sensitive littermate, the lean Zucker rat. (c) Pretreatment with tiron depressed vasoconstriction to phenylephrine and comparably enhanced the L-NAME-mediated leftward shift in contractile reactivity in the obese and lean Zucker rats in hydroquinone+buthionine sulfoximine-sensitive manner. (d) Our data therefore indicate superior endothelial function in the obese relative to the lean Zucker rat, reflected by a greater regulation of vasoconstrictor reactivity by basal NO, while the regulation of NO bioavailability by superoxide anion is similar.
Laight
D W
DW
School of Pharmacy and Biomedical Sciences, St. Michael's Building, University of Portsmouth, White Swan Road, Portsmouth PO1 2DT, UK. david.laight@port.ac.uk
Anggård
E E
EE
Carrier
M J
MJ
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006873:Hydroquinones / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D018384:Oxidative Stress / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000963:Antimetabolites; D000975:Antioxidants; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D014662:Vasoconstrictor Agents; D013481:Superoxides; D010656:Phenylephrine; D009569:Nitric Oxide; D019328:Buthionine Sulfoximine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; C031927:hydroquinone