Decreased ultrafiltration coefficient of glomeruli isolated from volume-depleted rats.
Decreased glomerular ultrafiltration coefficient (Kf or LpA) has been demonstrated in micropuncture studies of rats subjected to dietary sodium restriction and diuretics. To define the alterations in glomerular filtration characteristics in isolation from systemic hemodynamic influences, we studied filtration of isolated rat glomeruli in vitro. Control rats were maintained on standard laboratory chow and tap water until sacrifice. Experimental rats in groups I, II, and III were maintained on a sodium-deficient diet for 3 to 7 weeks. Further volume depletion was induced in groups II and III as follows: Group II rats were given furosemide, 30 mg/kg, intraperitoneally for 3 consecutive days prior to sacrifice; group III rats were given furosemide, 240 mg/kg, and killed (a) after about 4 hr when diuresis had resulted in 8% to 10% weight loss, (b) after 18 hr during which sodium restriction was continued, or (c) after 18 hr during which they were permitted to drink NaCl solution (0.9 gm/dl). Group IV rats were fed standard laboratory Chow and were subjected to hemorrhage of about 3% body weight and sacrificed after 18 hr of fasting. Plasma protein, serum creatinine and electrolytes, and FENa were measured in each rat prior to sacrifice. Filtration was induced in isolated glomeruli by applying a transcapillary oncotic gradient of about 12 mm Hg. A video recording of individual glomeruli was made during filtration, and glomerular diameter, volume, filtering surface area, Kf, and Lp were estimated from measurements of the video image. Kf was decreased during volume depletion induced by sodium restriction and furosemide or by hemorrhage. Kf averaged 4.0 +/- 0.2 nl/min . mm Hg in control rats (n = 10), 3.4 +/- 0.2 nl/min . mm Hg in group I (n = 8), 3.3 +/- 0.1 nl/min . mm Hg in group II (n = 12), 2.2 +/- 0.1 nl/min . mm Hg in group IIIa (n = 4), 2.6 +/- 0.3 nl/min . mm Hg in group IIIb (n = 4), and 2.3 +/- 0.2 nl/min . mm Hg in group IV (n = 3). Kf returned to control values after volume repletion with orally administered NaCl solution and averaged 4.3 +/- 0.3 nl/min . mm Hg in group IIIc (n = 4). We conclude that Kf falls in a graded and reversible fashion during volume depletion. Modulation of Kf, as well as previously described alterations in renal cortical perfusion, may contribute to decreased GFR in volume depletion.