Time-course of the alterations in prostanoid production and in contractile responses of mesenteric beds isolated from streptozotocin diabetic rats.
The prostanoid production and the effect of indomethacin on the noradrenaline-induced contractions were studied in the mesenteric bed of rats at different times (1-8 weeks) after the administration of streptozotocin (STZ). The production of prostacyclin (measured as 6-keto-PGF1alpha) and prostaglandin (PG) E2 was unchanged one week after STZ, but it was reduced to 50% of control values 4 weeks after STZ without further changes 8 weeks after the treatment. The release of thromboxane (TX) A2 (measured as TXB2) and PGF2alpha, increased by 100% one week after STZ and returned to basal values at 3 weeks. TX release was below control values 8 weeks after STZ. The ratio 6-keto-PGF1alpha/TXB2 was reduced one week after STZ, recovered to control values at 4 weeks and augmented at 8 weeks. Indomethacin (10 microM) reduced the contractile responses to noradrenaline in the controls, whereas in STZ-treated rats this effect was observed solely 8 weeks after the treatment. Since this recovery coincided with an increase of the vasodilator/vasoconstrictor prostanoid ratio, a time-dependent compensation of the vascular alterations caused by STZ can be proposed from the present results.
Instituto de Investigaciones Farmacológicas (ININFA, CONICET), Buenos Aires, Argentina. hperedo@huemul.ffyb.uba.ar
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Adler-Graschinsky
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013152:Splanchnic Circulation / Q000187:drug effects* / Q000502:physiology; D013929:Thromboxane B2 / Q000378:metabolism; D013997:Time Factors
D011453:Prostaglandins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D015232:Dinoprostone; D009638:Norepinephrine; D007213:Indomethacin