title: Flow- and acetylcholine-induced dilatation in small arteries from rats with renovascular hypertension--effect of tempol treatment.
abstract: We investigated whether renovascular hypertension alters vasodilatation mediated by nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) and the influence of the superoxide dismutase mimetic tempol on vasodilatation. One-kidney one-clip hypertensive Sprague-Dawley rats, treated with either vehicle or tempol (from weeks 5 to 10 after placement of the clip), and uninephrectomized control rats were investigated. In renal hypertensive rats systolic blood pressure increased to 171+/-6 mmHg (n=10), while in tempol-treated rats systolic blood pressure remained normal (139+/-7 mmHg, n=5). In isolated pressurized mesenteric small arteries NO-mediated dilatation was obtained by increasing flow rate and EDHF-mediated dilatation by acetylcholine. In arteries from hypertensive rats, flow-induced dilatation was blunted, as compared to normotensive and tempol-treated rats, while acetylcholine-induced dilatation remained normal. Measured by dihydroethidium staining there was an increased amount of superoxide in arteries from vehicle-treated rats, but not from tempol-treated rats. Expression by immunoblotting of endothelial NO synthase and the NAD(P)H oxidase subunit p47phox remained unaffected by high blood pressure and tempol treatment. Simultaneous measurements of NO-concentration and relaxation were performed in isolated coronary arteries from the same animals. As compared to vehicle-treated rats, both acetylcholine-induced relaxation and NO-concentration increased in arteries from tempol-treated animals, while only the relaxation was improved by the NO donor, S-nitroso-N-acetylpenicillamine (SNAP). In conclusion renovascular hypertension selectively inhibits flow-induced NO-mediated vasodilatation, while EDHF-type vasodilatation remains unaffected, suggesting that high blood pressure leads to increased generation of superoxide contributing to decreased NO bioavailability. Furthermore, the abnormal endothelium function can be corrected by tempol treatment, but this seems to involve mechanisms partly independent of NO.
authors.affiliation: Department of Pharmacology, University of Aarhus, 8000 Aarhus C, Denmark.
authors.forename: Frank Holden
authors.initials: FH
authors.lastname: Christensen
authors.forename: Edgaras
authors.initials: E
authors.lastname: Stankevicius
authors.forename: Thomas
authors.initials: T
authors.lastname: Hansen
authors.forename: Malene Munk
authors.initials: MM
authors.lastname: Jørgensen
authors.forename: Vanesa Lopez
authors.initials: VL
authors.lastname: Valverde
authors.forename: Ulf
authors.initials: U
authors.lastname: Simonsen
authors.forename: Niels Henrik
authors.initials: NH
authors.lastname: Buus
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D006978:Hypertension, Renovascular / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000502:physiology; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D020030:Nitric Oxide Donors; D013113:Spin Labels; D014665:Vasodilator Agents; D013481:Superoxides; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D000109:Acetylcholine; C001803:tempol