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

Abstract

We studied the relationships between acrachidonic 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. PGE 2 and PGF 2α produced a similar dose-dependent relaxation of mesenteric arteries from normal and diabetic dogs. On the contrary, NaA and prostacyclin (PGI 2) 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 A 2 (TXA 2) biosynthesis abolished in vitro the vasoconstricting effect of NaA and PGI 2 in diabetics whereas inhibitors of PGI 2 biosynthesis blocked the vasodilating influence of NaA in normal mesenteric vessels. Additionally, antagonists of cycooxygenase activity prevented both the vasoconstricting and the vasodilating actions of NaA in normal and in diabetic arteries, respectively, as well as the PGI 2 tone enhancement in vessels from diabetics. In arteries from pancreatectomized animals treated with insulin, PGI 2 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 TXB 2 than did vessels from intact normal control or sham-operated dogs. Moreover, in the presence of exogenous PGI 2, the vascular production of TXB 2 from AA in the diabetic group was significantly greater than that of preparations not exposed to PGI 2. The % conversion of AA into PGI 2 (assessed as 6-oxo-PGF 1α) was similar in normal controls, in sham-operated and in diabetic vessels. Insulin given in vivo abolished the greater basal conversion of AA into TBX 2 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 PGI 2 in mesenteric arteries from diabetic dogs could be related to the generation of TXA 2 by vessel walls.