Fatty acid inhibition of angiotensin II-stimulated inositol phosphates in smooth muscle cells.
Inositol phosphate (InsP) responses to angiotensin II (ANG II) stimulation were measured in cultured rat vascular smooth muscle cells (VSMC) incubated with and without fatty acids (FA). VSMC were washed after 24 h of FA incubation to achieve cellular incorporation of FA yet eliminate ambient FA. Incubation with eicosapentaenoic acid (EPA)-supplemented medium resulted in concentration-dependent incorporation of EPA and depletion of arachidonic acid in VSMC membranes. Incubation with EPA, but not other FA, resulted in inhibition of ANG II-stimulated InsP formation (29% inhibition with 100 microM EPA). In contrast, InsP formation in response to guanine nucleotide-binding protein stimulation was not affected by EPA. ANG II receptor binding to membranes prepared from EPA-loaded VSMC was 18% lower than binding in membranes from sham-loaded cells. In other studies, VSMC were exposed acutely to FA to avoid cellular incorporation. Exposure to all FA resulted in concentration-dependent reductions in ANG II binding and ANG II-stimulated InsP formation; binding affinity was reduced without changes in receptor density. We conclude that ANG II-stimulated InsP formation is modestly and selectively inhibited by EPA incorporation and more profoundly inhibited by acute exposure to many FA via interference with ANG II receptor binding.
Ullian
M E
ME
Department of Medicine, Medical University of South Carolina, Charleston 29425.
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000037:antagonists & inhibitors*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D051381:Rats
D005227:Fatty Acids; D007295:Inositol Phosphates; D000804:Angiotensin II