Role for angiotensin II in an overt functional proteinuria.
A partial renal vein constriction (RVC) was induced acutely in Munich-Wistar rats. RVC caused a marked reduction in glomerular plasma flow rate, and rises in glomerular transcapillary hydraulic pressure difference and efferent arteriolar resistance. These changes were associated with a marked increase in urinary protein excretion, on average from a baseline level of 8 to approximately 120 mg/24 hrs per kidney. Infusion of saralasin, an angiotensin II (AII) antagonist, largely normalized these indices, including urinary protein excretion (to approximately 35 mg/24 hrs per kidney), despite continued RVC. In separate rats, fractional clearances of neutral [125I]dextrans (molecular radii = 18-60 A) (CDEX/CIN) were measured. RVC caused a significant increase in CDEX/CIN for large dextrans (greater than or equal to 44A), but not small dextrans (less than or equal to 42A). Saralasin infusion led to a partial return toward baseline values of CDEX/CIN for the large dextrans. On the basis of the heteroporous membrane theory for glomerular filtration, the glomerular sieving defect during RVC was attributed to an increase in the relative fluid flux through a group of large non-selective pores. A marked alteration in glomerular microcirculatory pattern induced by enhanced action of endogenous AII in turn seemed to account largely, although not entirely, for the impairment of glomerular size-selectivity during RVC.
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology; D003250:Constriction; D003911:Dextrans / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D008970:Molecular Weight; D011312:Pressure; D011507:Proteinuria / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012082:Renal Veins / Q000502:physiology; D012504:Saralasin / Q000494:pharmacology
D003911:Dextrans; D000804:Angiotensin II; D012504:Saralasin