Glomerular dysfunction induced by polymorphonuclear leukocyte-derived reactive oxygen species.
The role of reactive oxygen species (ROS) derived from polymorphonuclear leukocytes (PMN) on glomerular microcirculation was evaluated in Munich-Wistar rats. To induce local activation of PMN, phorbol myristate acetate (PMA, 20 micrograms) was infused unilaterally into the renal artery in six rats and the micropuncture study was performed 18 h later. In these animals, there was a significant (P less than 0.005) glomerular PMN accumulation in the PMA-injected kidney (on average 2.2 +/- 0.2 per 3-microns glomerular section) compared with the contralateral kidneys of the same rats or the vehicle-treated kidneys from a separate group of seven rats (0.2 +/- 0.1 and 0.2 +/- 0.1 per 3-microns glomerular section, respectively). In the PMA-treated kidneys, whole kidney glomerular filtration rate (GFR) was significantly reduced compared with that of the contralateral kidney of the same rats or vehicle-treated kidneys of a separate group of rats (0.61 +/- 0.04, 1.18 +/- 0.05, and 1.02 +/- 0.04 ml/min, respectively, P less than 0.05). This PMA-induced reduction in GFR was largely prevented by pretreatment of rats with a scavenger of hydrogen peroxide, catalase (1,000 kU; n = 7), or by depletion of PMN with an intravenous nitrogen mustard administration (1.7 mg/kg; n = 7). The reduction of GFR in the PMA-treated kidneys therefore appeared to be mediated by the ROS derived from activated PMN. The micropuncture measurement of glomerular microcirculatory dynamics in PMA-treated kidneys without above pretreatment revealed that there was a profound fall in single-nephron GFR and ultrafiltration coefficient and an increase in renal arteriolar resistances (greater in efferent than afferent arteriole).(ABSTRACT TRUNCATED AT 250 WORDS)
Yoshioka
T
T
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2584.
Ichikawa
I
I
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008833:Microcirculation; D009504:Neutrophils / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014661:Vasoconstriction
D002374:Catalase; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen