title: Platelet-activating factor mediates angiotensin II-induced proteinuria in isolated perfused rat kidney.
abstract: Isolated kidney preparations (IPK) from male Sprague Dawley rats perfused at constant pressure were used to evaluate the effect of angiotensin II (AII) and platelet-activating factor (PAF) on renal function and urinary protein excretion. Compared with basal, intrarenal infusion of AII at 8 ng/min caused a progressive increase in protein excretion (11 +/- 6 versus 73 +/- 21 micrograms/min) in parallel with a decline in renal perfusate flow (RPF) (29 +/- 3 versus 18 +/- 3 ml/min). Addition to the perfusate of PAF at 50 nM final concentration also induced proteinuria (9 +/- 4 versus 55 +/- 14 micrograms/min) but did not change RPF (29 +/- 3 versus 30 +/- 3 ml/min). Preexposure of isolated kidneys to the PAF receptor antagonist WEB 2086 prevented the increase in urinary protein excretion induced by AII infusion (basal: 13 +/- 6; post-AII: 12 +/- 7 micrograms/min) but failed to prevent the vasoactive effect of AII (RPF, basal: 30 +/- 2; post-AII: 21 +/- 3 ml/min). In additional experiments, dexamethasone reduced the proteinuric effect of PAF remarkably. These results indicate that in isolated kidney preparation: (1) AII infusion induced proteinuria and decreased RPF; and (2) the effect of AII in enhancing urinary protein excretion was completely prevented by a specific PAF receptor antagonist, which, however, did not influence the AII-induced fall in RPF. It is suggested that PAF plays a major role in AII-induced changes in the permselective function of the glomerular capillary barrier.
authors.affiliation: Mario Negri Institute for Pharmacological Research, Ospedali Riuniti di Bergamo, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Perico
authors.forename: R
authors.initials: R
authors.lastname: Lapinski
authors.forename: K
authors.initials: K
authors.lastname: Konopka
authors.forename: S
authors.initials: S
authors.lastname: Aiello
authors.forename: M
authors.initials: M
authors.lastname: Noris
authors.forename: G
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D010477:Perfusion; D010972:Platelet Activating Factor / Q000494:pharmacology / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011507:Proteinuria / Q000139:chemically induced* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles / Q000494:pharmacology
chemical_list: D001381:Azepines; D005938:Glucocorticoids; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; D000804:Angiotensin II; D003907:Dexamethasone