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-PGF1 alpha) and prostaglandin (PG) E-2 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) A(2) (measured as TXB2) and PGF(2 alpha), 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-PGF(1 alpha)/TXB2 was reduced one week after STZ, recovered to control values at 4 weeks and augmented at 8 weeks. Indomethacin (10 mu M) 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.