Augmented thromboxane generation by mesenteric arteries from pancreatectomized diabetic dogs is coincident with the vascular tone enhancement evoked by Na arachidonate and prostacyclin.

We studied the relationships between arachidonic acid (AA) metabolism and contractile responses to Na arachidonate (NaA) and the prostaglandins (PGs) in mesenteric arteries isolated from sham-operated and totally pancreatectomized dogs. PGE2 and PGF2 alpha produced a similar dose-dependent relaxation of mesenteric arteries from normal and diabetic dogs. On the contrary, NaA and prostacyclin (PGI2) enhanced the resting basal tone of arteries from pancreatectomized animals but depressed it in arteries from intact normal control or from sham-operated groups. Inhibitors of thromboxane A2 (TXA2) biosynthesis abolished in vitro the vasoconstricting effect of NaA and PGI2 in diabetics whereas inhibitors of PGI2 biosynthesis blocked the vasodilating influence of NaA in normal mesenteric vessels. Additionally, antagonists of cyclooxygenase activity prevented both the vasoconstricting and the vasodilating actions of NaA in normal and in diabetic arteries, respectively, as well as the PGI2 tone enhancement in vessels from diabetics. In arteries from pancreatectomized animals treated with insulin, PGI2 induced a biphasic (constriction and relaxation) effect of a magnitude between that of effects seen in normal controls or sham-operated and those in untreated diabetic animals. The basal radioconversion of exogenous [1-14C]AA, showed that mesenteric arteries from diabetic dogs generated more TXB2 than did vessels from intact normal control or sham-operated dogs. Moreover, in the presence of exogenous PGI2, the vascular production of TXB2 from AA in the diabetic group was significantly greater than that of preparations not exposed to PGI2. The % conversion of AA into PGI2 (assessed as 6-oxo-PGF1 alpha) was similar in normal controls, in sham-operated and in diabetic vessels. Insulin given in vivo abolished the greater basal conversion of AA into TBX2 by mesenteric arteries from diabetic dogs and significantly attenuated the enhanced prostacyclin-evoked generation of thromboxane. The present results strongly suggest that the abnormal constricting response evoked by NaA and PGI2 in mesenteric arteries from diabetic dogs could be related to the generation of TXA2 by vessel walls.