Renal effects and mesangial cell contraction induced by endothelin are mediated by PAF

Renal effects and mesangial cell contraction induced by endothelin are mediated by PAF. The recently discovered vasoactive peptide endothelin and platelet activating factor (PAF) share similar renal effects. The purpose of the present series of experiments has been to analyze the functional relations between the effect of endothelin on renal function and glomerular and mesangial cell contraction and the production and actions of PAF in kidney. Endothelin 1 nmol/kg body wt induced a transient decrease of glomerular filtration rate (from 1.99 ± 0.17 to 0.56 ± 0.18 ml/min) and renal blood flow (from 10.8 ± 1.3 to 2.7 ± 0.3 ml/min). Endothelin also induced a marked reduction of planar cell surface area of cultured mesangial cells (30 ± 5%) and of cross sectional area of isolated glomeruli (from 1.51 ± 0.02 to 1.31 ± 0.02m2 × 10-8). BN-52021 or WEB-2170, two potent specific inhibitors of PAF receptor binding, blocked the effects of endothelin on renal function and on the contraction of isolated glomeruli and mesangial cells. In addition, endothelin induced a significant increase in the production of PAF by isolated glomeruli (Basal, 81 ± 10 pg/mg protein; endothelin, 10-7 M, 140 ± 18 pg/mg protein). Endothelin also stimulated the incorporation of [3H]acetate into PAF, both in glomeruli (264.27 ± 27.7%) and mesangial cells (251 ± 41%). These effects were blocked by EGTA and by verapamil. Our results suggest that PAF may be a mediator of the effects of endothelin on renal function and glomerular and mesangial cell contraction