Angiotensin II modulates glomerular capillary permselectivity in rat isolated perfused kidney.
Studies in experimental animals and humans have documented that inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitors reduces urinary protein excretion rate and retards the development of renal injury. Here we sought to investigate whether angiotensin II (All) modified the size-selective properties to macromolecules of the glomerular capillary barrier in isolated perfused rat kidney preparation. Compared with basal values, continuous All infusion into the renal artery at the rate of 3 or 8 ng/min, but not at 0.6 ng/min, induced a progressive and significant increase in urinary protein excretion rate. Evaluation of the sieving properties of the glomerular barrier by fractional clearance of polydisperse Ficoll showed that All significantly enhanced the filtration of tracer molecules of radil > or = 34A. All-induced changes in urinary protein excretion rate and in Ficoll fractional clearance were completely prevented by pretreatment with the specific All Type 1 receptor antagonist SR 47436.
Lapinski
R
R
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Perico
N
N
Remuzzi
A
A
Sangalli
F
F
Benigni
A
A
Remuzzi
G
G
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D005362:Ficoll / Q000493:pharmacokinetics; D000077405:Irbesartan; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008970:Molecular Weight; D010316:Particle Size; D010477:Perfusion; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000804:Angiotensin II; D005362:Ficoll; D000077405:Irbesartan