RENIN RESPONSE TO 12-HYDROXYEICOSATETRAENOIC ACID IS INCREASED IN DIABETIC RATS

Eicosanoids (prostagtandins) can alter renin secretion and angiotensin (ANG) II action. We have studied the effects of both prostacyclin and a lipoxygenase (LO) product, 12-hydroxyeicosatetraenoic acid (12-HETE ), on renin in normal and streptozotocin-induced diabetic rats. 12-HET E is not only a potent inhibitor of basal renin secretion but also a k ey mediator of ANG II-induced renin inhibition, We have also examined the effects of ANG II on 12-HETE formation in normal and diabetic anim als. Both plasma (3.9 +/- 0.9 vs. 0.8 +/- 0.1 ng ANG I . ml(-1). h(-1) , P < 0.01) and tissue (38 +/- 6 vs. 21 +/- 2 ng ANG I . mg tissue(-1) . h(-1), P < 0.05) renin activity levels were markedly reduced in diab etic animals. Iloprost (10(-6) mol/l), a stable analog of prostacyclin , had similar stimulatory effects on renin secretion in both normal an d diabetic tissues, but the response was enhanced by LO inhibition in diabetic tissue. 12-HETE (10(-7) mol/l) had an exaggerated effect on r enin inhibition in diabetic tissue (78 +/- 2% normal vs. 65 +/- 4% dia betic, P < 0.05), Similarly, ANG II (10(-8) mol/l) inhibition of renin was significantly enhanced in diabetic rats (P < 0.001). However, ANG II did not produce an exaggerated increase in 12-HETE in diabetic ren al tissue. Insulin reversed the inhibitory effects of ANG II on renin in normal rats, but it blunted the effect of ANG II in diabetic rats. These studies suggest that, while the capacity of renal cortical tissu e to synthesize 12-HETE in response to ANG II is not altered, 12-HETE and ANG II actions are exaggerated in diabetes, and this may contribut e to reduced renin production.