No abstract

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 +/- 0.02 m2 x 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.

Renal metabolism has been studied in eight dogs before and 48 hr after a 60-min period of renal ischemia induced by clamping the left renal artery with the simultaneous removal of the right kidney, and in 12 sham-operated animals. The study involved the measurement of renal uptake and production of lactate, glutamine, glutamate, alanine, ammonium, and oxygen, and the measurement of the tissue concentrations of ATP, glutamine, lactate, alpha-ketoglutarate, aspartate, and alanine in the renal cortex. Two days after a temporary renal ischemia, the remaining kidney showed a 22% decrease in glomerular filtration rate (GFR) and a 25% decrease in renal plasma flow. Fractional sodium and potassium excretions were similar to those of control dogs. Renal production or extraction of glutamine, glutamate, alanine, ammonium, and oxygen (all expressed by 100 ml of GFR) was not significantly different in basal conditions or 2 days after ischemia, but lactate extraction was reduced in postischemic kidneys (-101 +/- 29 vs -204 +/- 38 mumol/100 ml GFR in control dogs). The cortical concentrations of glutamine and glutamate were lower in postischemic than in control kidneys. No differences were found in cortical concentration of alpha-ketoglutarate, aspartate, lactate, pyruvate, or ATP, but total nucleotides and inorganic phosphate were decreased in postischemic kidneys. It is concluded that in the recovery phase of the ischemia, a decreased lactate uptake is the main metabolic change, and total ATP production is adapted to the decrease of GFR and sodium reabsorption.