Effect of streptozotocin-induced diabetes on prostaglandin production by rat cerebral microvessels.
Diabetes has been shown to result in reduced prostacyclin synthesis by macrovascular tissue in rats and humans. Other studies have shown that plasma levels of 6-keto-prostaglandin-F1 alpha (6-keto-PGF1 alpha) and synthesis of 6-keto-PGF1 alpha by isolated glomeruli are either unchanged or increased in diabetes. Thus, microvascular tissue may respond differently to diabetes than macrovascular tissue. Accordingly, we have studied the effects of streptozotocin-induced diabetes mellitus on prostaglandin synthesis by rat cerebral microvessel (RCMV). Prostaglandin synthesis from both endogenous and exogenous arachidonic acid was determined. The yield of RCMV from diabetic and control animals was similar. Under basal conditions and following stimulation of prostaglandin synthesis by melittin (5 micrograms/ml), RCMV production of prostacyclin (measured as immunoreactive 6-keto-PGF1 alpha) was greater than production of PGE2. Both 6-keto-PGF1 alpha and PGE2 production under basal and stimulated conditions were found to be similar for control and diabetic RCMV. The RCMV converted exogenous [3H]arachidonic acid predominately to PGD2 and to a lesser extent to 6-keto-PGF1 alpha. No significant differences in the conversion of exogenous [3H]arachidonic acid to PGD2 and 6-keto-PGF1 alpha was observed between control and diabetic RCMV. This study suggests that the effect of streptozotocin-induced diabetes mellitus on prostaglandin formation by microvascular endothelium is different from its effect on macrovascular tissue.
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000378:metabolism; D011464:Epoprostenol / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D008555:Melitten / Q000494:pharmacology; D008833:Microcirculation / Q000378:metabolism; D011458:Prostaglandins E / Q000032:analysis / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin; D013997:Time Factors
D011458:Prostaglandins E; D008555:Melitten; D013311:Streptozocin; D011464:Epoprostenol; D015232:Dinoprostone