Diabetes-induced enhancement of prostanoid-stimulated contraction in mesenteric veins of mice.
We investigated the influence of the diabetic state on the contractile response of longitudinal segments of isolated mesenteric vein to prostanoids and leukotriene (LT), and the contribution of the vascular endothelium to modulation of the contractile response was determined. The normal mesenteric vein and de-endothelialized veins of normal (ddY), diabetic KK-CAy and streptozotocin ddY mice (150 mg/kg, i.v., 6 weeks) were used. In the diabetic state, the contractions produced by noradrenaline (60 microM), high K+ solution (143.4 mM), and the thromboxane A2 analogue U-46619 (29 nM-29 mM) were not affected, and LTD4 (0.1 nM-1 microM)-induced contraction was suppressed. Contractions induced by prostaglandin (PG) E2 (0.2 microM-2 mM), PGF2 alpha (0.3 microM-0.3 mM) and the prostacyclin derivatives PGI2-Na (10-100 microM) and TRK-100 (0.2 microM-2 mM) were significantly enhanced in the presence of an intact vascular endothelium, but not in de-endothelialized segments. The increase in PGF2 alpha (0.28 mM) contractions was dependent on age (correlation coefficient r = 0.36, significant difference, P less than 0.05) and blood glucose (r = 0.88, significant difference, P less than 0.01), but was independent of obesity. The contractile response to PGD2 (0.3-0.9 mM) was enhanced in both intact and de-endothelialized segments. These results indicate that the diabetic state affects prostanoid responses in an endothelium-dependent manner, except for the PGD2 response, which is independent of the endothelium.
Kimura
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I
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Pancho
L R
LR
Isoi
Y
Y
Kimura
M
M
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D015237:Dinoprost / Q000494:pharmacology; D004727:Endothelium / Q000166:cytology; D005260:Female; D015289:Leukotrienes / Q000494:pharmacology; D008297:Male; D008642:Mesenteric Veins / Q000502:physiology*; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D013931:Thromboxanes / Q000494:pharmacology
D015289:Leukotrienes; D011453:Prostaglandins; D013931:Thromboxanes; D015237:Dinoprost; D011188:Potassium; D009638:Norepinephrine