Rapid, dynamic changes in glomerular permeability to macromolecules during systemic Angiotensin II (AngII) infusion in rats.

• The actions of systemic angiotensin II (AngII) infusions on glomerular permeability were investigated in vivo. In anaesthetized Wistar rats (250-280g) the left ureter was cannulated for urine collection, while simultaneously blood access was achieved. Rats were continuously infused i.v. with either of four doses of AngII (16 ng/kg/min (Lo-AngII; n=7), 230 ng/kg/min (Lo-Int-AngII; n=8), 910 ng/kg/min (Hi-Int-AngII; n=7), or 1.82 μg/kg/min (Hi-AngII; n=8)), or with the calcium channel blocker, nimodipine, together with the Hi-Int-AngII dose (n=6), respectively, and with polydisperse fluorescein isothiocyanate (FITC)-Ficoll-70/400 (mol.radius 10-80Å) and (51)Cr-EDTA. Plasma and urine samples were taken at 5, 15, 30, 60 and 120 min and analyzed by high performance size exclusion chromatography (HPSEC) for determination of glomerular sieving coefficients (θ) to Ficoll. Mean arterial pressure (MAP) and glomerular filtration rate (GFR) were also assessed. In AngII groups there was a rapid, marked increase in glomerular permeability (θ) to Ficoll molecules >34Å, which was completely abrogated by the AngII-blocker, candesartan. The permeability increase was reversible within 15-60 min, but some increases remained even after 60 min. For the highest AngII doses given GFR decreased transiently, concomitant with marked increases in MAP. Nimodipine blocked the hemodynamic AngII actions, whereas the glomerular permeability response remained unchanged. According to a two-pore model and a log-normal distributed pore model the AngII induced increases in glomerular permeability are compatible with an increased number of "large pores" in the glomerular filter, and, to some extent, an increase in the dispersity of the small pore radius.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Urology and Nephrology (hsv//eng)

Nyckelord

Ficoll

glomerular filtration

microalbuminuria

sieving coefficients

log-normal distributed pore model

aldosterone

podocytes

nimodipine

candesartan

spironolactone

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