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.
Copyright © 2011 S. Karger AG, Basel.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
-
Acetylcholine / pharmacology
-
Animals
-
Blood Pressure
-
Bridged Bicyclo Compounds, Heterocyclic
-
Disease Models, Animal
-
Dose-Response Relationship, Drug
-
Drug Evaluation, Preclinical
-
Endothelium, Vascular / physiopathology
-
Epinephrine / pharmacology
-
Fatty Acids, Unsaturated
-
Hydrazines / pharmacology
-
Hypertension / genetics
-
Hypertension / physiopathology*
-
Hypoglycemic Agents / pharmacology*
-
Indomethacin / pharmacology
-
Male
-
Mesenteric Arteries / physiopathology*
-
Muscle, Smooth, Vascular / physiopathology
-
NG-Nitroarginine Methyl Ester / pharmacology
-
Nitroprusside / pharmacology
-
Pioglitazone
-
Rats
-
Rats, Inbred SHR
-
Rats, Inbred WKY
-
Rosiglitazone
-
Thiazolidinediones / pharmacology*
-
Thromboxane A2 / metabolism
-
Vascular Resistance / drug effects*
-
Vascular Resistance / physiology
-
Vasoconstrictor Agents / pharmacology
-
Vasodilator Agents / pharmacology
Substances
-
Bridged Bicyclo Compounds, Heterocyclic
-
Fatty Acids, Unsaturated
-
Hydrazines
-
Hypoglycemic Agents
-
Thiazolidinediones
-
Vasoconstrictor Agents
-
Vasodilator Agents
-
Rosiglitazone
-
Nitroprusside
-
Thromboxane A2
-
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
-
SQ 29548
-
Acetylcholine
-
NG-Nitroarginine Methyl Ester
-
Pioglitazone
-
Indomethacin
-
Epinephrine