Vascular responsiveness and eicosanoid production in diabetic rats

Vascular responsiveness to vasoactive eicosanoids as well as vascular prostacyclin and thromboxane production was investigated in 7-10 weeks alloxan-diabetic rats. Aortic rings from diabetic rats exhibited increased responsiveness to carbocyclic thromboxane A2, a thromboxane analogue, when compared to control rat aortae. Isolated perfused hearts of diabetic rats showed increased vascular responsiveness to 9,11-methanoepoxy PGH2 (U-46619), an endoperoxide analogue. Diabetes resulted in a reduction in prostacyclin generation by isolated incubated aortae which was overcome by the addition of arachidonic acid but not by homogenization of incubated aortic tissue. In contrast, prostacyclin, but not thromboxane, generation was elevated in isolated perfused hearts of diabetic animals in response to moderate doses of arachidonic acid, but at high doses of arachidonate, more thromboxane was formed by perfused hearts of diabetic rats. These results suggest that different vessels can either increase or decrease their prostaglandin production in response to diabetes. The alterations in prostanoid production may be due to differential changes in prostacyclin and thromboxane synthesis in vessels which, in turn, may be related to the changes in vascular responsiveness.