Angiotensin II causes formation of platelet activating factor in cultured rat mesangial cells.
Angiotensin II may contribute to the progression of renal glomerular diseases. Beneficial effects of converting enzyme inhibition in models of renal disease are, however, not always explicable by hemodynamic consequences of angiotensin II inhibition. Angiotensin increases intracellular calcium in glomerular mesangial cells and activates phospholipase A2, factors required for the formation of the lipid mediator of inflammation platelet activating factor (PAF). We therefore examined whether angiotensin II could stimulate PAF production in cultured rat mesangial cells. During a 15-minute incubation angiotensin II caused formation of PAF in a dose-dependent manner with a threshold around 10(-9) M. In four experiments PAF formation in response to angiotensin II (10(-8) M) occurred within 5 minutes and was 29 +/- 8 pmol PAF/mg protein. The amount of PAF detected then declined to 9 +/- 2 and 13 +/- 3 pmol after 15 and 30 minutes of incubation with angiotensin II. More than 90% of the PAF remained cell-associated. The PAF formation was confirmed by negative ion chemical ionization mode of mass spectrometry. A single species of PAF was detected and identified as hexadecyl PAF. We speculate that part of the detrimental effects of angiotensin II in progressive renal disease may relate to PAF formation. The PAF generated may in turn influence glomerular function, platelets, and eicosanoid synthesis, all factors implicated in renal disease. Furthermore, we speculate that angiotensin II-induced PAF formation may contribute to microvasculature pathology in general.
Neuwirth
R
R
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
Satriano
J A
JA
DeCandido
S
S
Clay
K
K
Schlondorff
D
D
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001681:Biological Assay; D002478:Cells, Cultured; D008401:Gas Chromatography-Mass Spectrometry; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats
D010972:Platelet Activating Factor; D000804:Angiotensin II