title: Effects of pioglitazone and rosiglitazone on vascular function of mesenteric resistance arteries in rat genetic hypertension.
abstract: Glitazones exhibit beneficial effects in the vascular system, both on large vessels and at a microcirculatory level. We previously reported the effects of glitazones in the aorta of spontaneously hypertensive rats (SHR). We focus now on the acute and long-term actions of these drugs on mesenteric resistance arteries of the SHR. Incubation with pioglitazone or rosiglitazone (10⁻⁵ mol/l) improved endothelium-dependent relaxations to acetylcholine and the endothelial modulation of phenylephrine contractions. Acetylcholine relaxations that were abolished by N(G)-nitro-L-arginine methylester were partly recovered by the glitazones, but no effects of these drugs were observed in the presence of indomethacin or indomethacin + L-NAME. Glitazones did not change the contractions to U46619 or the endothelium-independent relaxation to sodium nitroprusside. Three-week oral pioglitazone or rosiglitazone treatment (3 and 10 mg/kg/day, respectively) confirmed the acute experiments. Thus, in microvessels, glitazones improve endothelial function in such a way that they do not alter endothelial nitric oxide release but reduce the production of vasoconstrictor prostanoids from endothelial cells.
authors.affiliation: Department of Medical Sciences, University of Castilla-La Mancha, School of Medicine and Regional Centre for Biomedical Research, Albacete, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Mendizábal
authors.forename: Sílvia
authors.initials: S
authors.lastname: Llorens
authors.forename: Eduardo
authors.initials: E
authors.lastname: Nava
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000503:physiopathology; D004837:Epinephrine / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D000077205:Pioglitazone; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000077154:Rosiglitazone; D009599:Nitroprusside; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D000077205:Pioglitazone; D007213:Indomethacin; D004837:Epinephrine