ROLE OF THE LIPOXYGENASE PATHWAY IN ANGIOTENSIN-II-INDUCED VASCULAR SMOOTH-MUSCLE CELL HYPERTROPHY

The 12-lipoxygenase pathway is a key mediator of angiotensin II (Ang I I)-induced effects in the adrenal cortex We also recently demonstrated that Ang II increases 12- and 15-lipoxygenase product levels in vascu lar smooth muscle cells. However, the relation between lipoxygenase ac tivation and Ang II-induced vascular smooth muscle cell hypertrophy is not known. We studied the effects of Ang II and 12-lipoxygenase produ cts on both total cell protein content and the levels of the matrix pr otein fibronectin in quiescent porcine aortic smooth muscle cells. Ang II-induced increases in cellular protein content were attenuated by t he specific 12-lipoxygenase inhibitor baicalein; in contrast, the cycl oxygenase inhibitor ibuprofen had no effect. Direct addition of the 12 -lipoxygenase product 12-S-hydroxyeicosatetraenoic acid increased tota l cell protein content. We have recently shown that porcine vascular s mooth muscle cell growth is potentiated in high glucose (25 mmol/L) cu lture conditions. We observed that both Ang II and 12-S-hydroxyeicosat etraenoic acid induced a greater increase in protein content in cells cultured for two passages in high glucose. Furthermore, Ang II and 12- S-hydroxyeicasatetraenoic acid also markedly increased fibronectin lev els in cells cultured in high glucose. These results suggest that 12-l ipoxygenase activation plays a key role in Ang II-induced vascular smo oth muscle cell hypertrophy. Furthermore, both Ang II and lipoxygenase effects are enhanced in cells cultured under hyperglycemic conditions .