Elevated glucose in vivo and in vitro adversely alters prostaglandin generation in rat aortas and platelets.
An imbalance in prostacyclin (PGI2) and thromboxane (TXA2) generation from arachidonic acid (AA) may contribute to the marked increase in susceptibility to cardiovascular disease seen in diabetics. Rats made diabetic with streptozocin, and subsequently treated with saline or insulin, yielded aortic rings that synthesized decreasing amounts of PGI2 and platelets that generated increasing amounts of TXA2 in proportion to the degree of hyperglycemia. These alterations in AA metabolism were mimicked by incubating aortic rings or platelets from normal rats in buffer containing elevated glucose concentrations. Platelets incubated in elevated glucose displayed shorter times to maximal aggregation and higher percent maximal aggregation. Incubation of tissue in a buffer made hyperosmotic with mannitol had no effect on PGI2 or TXA2 formation, or platelet aggregation. These data suggest that hyperglycemia is involved in the PGI2/TXA2 imbalance and platelet abnormalities seen in diabetes, and reinforces the importance of rigid control of blood glucose as an approach to minimizing the incidence of diabetic cardiovascular complications.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D013928:Thromboxane A2 / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism
D001786:Blood Glucose; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D005947:Glucose