Altered arachidonic acid metabolism impairs functional vasodilation in metabolic syndrome.
These studies tested the hypothesis that in obese Zucker rats (OZRs), a model of metabolic syndrome, the impaired functional vasodilation is due to increased thromboxane receptor (TP)-mediated vasoconstriction and/or decreased prostacyclin-induced vasodilation. Spinotrapezius arcade arterioles from 12-wk-old lean (LZR) and OZR were chosen for microcirculatory observation. Arteriolar diameter (5 LZR and 6 OZR) was measured after 2 min of muscle stimulation in the absence or presence of 1 microM SQ-29548 (TP antagonist). Additionally, arteriolar diameter (6 for each group) was measured after application of iloprost (prostacyclin analog; 0.28, 2.8, and 28 microM), arachidonic acid (10 microM), and sodium nitroprusside (0.1, 1, and 10 microM) in the absence or presence of 1 microM SQ-29548. A 10 microM concentration of adenosine was used to induce a maximal dilation. Basal diameters were not different between LZRs and OZRs. Functional hyperemia and arachidonic acid-mediated vasodilations were significantly attenuated in OZR compared with LZR, and treatment with 1 microM SQ-29548 significantly enhanced the dilations in OZRs, although it had no effect in LZRs. Vasodilatory responses to iloprost and sodium nitroprusside (1 and 10 microM) were significantly reduced in OZR. Adenosine-mediated vasodilation was not different between groups. These results suggest that the impaired functional dilation in the OZR is due to an increased TP-mediated vasoconstriction and a decreased PGI2-induced vasodilation.
Xiang
Lusha
L
Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State St., Jackson, MS 39216-4505, USA.
Naik
Jay S
JS
Hodnett
Benjamin L
BL
Hester
Robert L
RL
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001160:Arterioles / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D016285:Iloprost / Q000494:pharmacology; D024821:Metabolic Syndrome / Q000378:metabolism / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D009765:Obesity / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D014665:Vasodilator Agents; D009599:Nitroprusside; D016718:Arachidonic Acid; C045749:SQ 29548; D016285:Iloprost