Single Nephron Filtration Fraction Research Articles

Glomerular dynamics and morphology of aged spontaneously hypertensive rats. Effects of angiotensin-converting enzyme inhibition.

Relationships between glomerular dynamics and renal injury, micropuncture and histological studies were assessed in 73 week-old normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats divided into untreated and angiotension-converting enzyme inhibitor-treated (quinapril; 3 mg/kg/day; for 3 weeks) groups. Urinary protein excretion (UPE) and histologic arteriolar (AIS) and glomerular (GIS) injury scores were determined. Mean arterial pressure (MAP) of untreated SHR was increased compared with WKY (200 +/- 6 vs 119 +/- 4 mm Hg; P < 0.01), effective renal plasma flow (ERPF) was reduced (1.47 +/- 0.21 vs 3.06 +/- 0.26 ml/min/per g; P > 0.01), and filtration fraction (FF) and total renal vascular resistance (RVR) of SHR were increased (P < 0.01). Single-nephron plasma flow (SNPF) of untreated SHR was decreased (174 +/- 17 vs 80 +/- 9 ml/min; P < 0.01), and single-nephron filtration fraction and afferent arteriolar resistance (RA) were increased (19.4 +/- 1.8 vs 30.0 +/- 2.5% and 1.90 +/- 0.25 vs 9.05 +/- 1.35 U, respectively; both P < 0.01). Despite reduced SNPF, glomerular capillary pressure (PG) increased (49.7 +/- 0.7 vs 53.8 +/- 1.3 mm Hg; P < 0.05), the result of efferent arteriolar constriction (1.15 +/- 0.18 vs 2.84 +/- 0.36 U; P < 0.01). Untreated SHR had higher UPE (13.9 +/- 1.5 vs 42.8 +/- 3.2; mg/100 g per day; P < 0.01) and GIS and AIS scores than WKY (4.3 +/- 1.1 vs 64.3 +/- 8.4 and 16.6 +/- 3.1 vs 96.3 +/- 14.4; both P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Intrarenal Hemodynamics in Low- and High-Output Cardiac Failure in Rats

Cardiac failure is multifactorial in causation, and the underlying physiologic mechanisms are variable, yet their renal effects have been considered more homogeneous. To investigate and compare the intrarenal hemodynamic characteristics in two experimental types (low- and high-output) of cardiac failure, renal micropuncture studies were performed in rats after myocardial infarction (MI) and arteriovenous fistula, respectively. Myocardial infarction was produced by ligation of the left main coronary artery and arteriovenous fistula by direct puncture of the aorta and inferior vena cava below the renal arteries. Pressures and interrenal and glomerular dynamics were obtained using classic micropuncture techniques. Both forms of cardiac failure were characterized by elevated left ventricular end-diastolic pressure (LVEDP), reduced mean arterial pressure, and increased cardiac mass. Left ventricular end-diastolic pressure was higher in MI rats, and effective renal plasma flow (ERPF) tended to be reduced in both forms of cardiac failure. There were no apparent differences in effective renal plasma flow between two models. In addition, single-nephron plasma flow and single-nephron glomerular filtration rate were reduced, and single-nephron filtration fraction and glomerular capillary pressure (PG) were increased in both models. These changes were associated with higher afferent and efferent arteriolar resistances and lower ultrafiltration coefficients. Despite these similarities, PG was higher in MI rats, yet LVEDP correlated directly with PG (r = 0.73; P < 0.001) and efferent arteriolar resistances (r = 0.72; P < 0.01). Therefore, although systemic arterial pressure and effective renal plasma flow were similar in both models of cardiac failure, PG was significantly higher in MI rats with higher LVEDP than in arteriovenous fistula rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of kinin and prostaglandin inhibitors on the renal response to angiotensin-converting enzyme inhibition: a micropuncture study in the dog.

It has been suggested that angiotensin-converting enzyme (ACE) inhibition is accompanied by enhanced bradykinin and prostaglandin activities, which may contribute to the renal haemodynamic actions of ACE inhibitors. Therefore we investigated renal function by clearance and micropuncture techniques in dogs maintained either on normal or low-salt diet before and after ACE inhibition with an i.v. bolus of 0.1 mg/kg ramiprilat followed by an infusion of 5 micrograms kg-1 min-1. Subgroups each comprising six dogs were also treated with either HOE-140, a bradykinin B2 receptor antagonist, or the cyclooxygenase inhibitor indomethacin. In general, renal effects of ramiprilat were more pronounced in dogs fed on low salt than in those on normal diet. In dogs on low salt, the mean arterial pressure decreased by 20% 20 min after ramiprilat application, whereas the total renal blood flow rose by 71% from 4.71 to 8.06 ml min-1 g kidney weight-1 and the glomerular filtration rate (GFR) by 28% from 0.74 to 0.95 ml min-1 g-1. Single-nephron glomerular blood flow and single-nephron GFR rose by 55% and 23% respectively. The total and the single-nephron filtration fraction decreased by 25% and 23% respectively. There were no substantial changes in glomerular and peritubular capillary and tubular pressures, but a significant increase in the ultrafiltration coefficient, Kf, by 103% from 3.55 nl/mmHg to 7.19 nl/mmHg (26.7-54.0 nl/kPa) was observed. Afferent and efferent arteriolar resistances decreased in parallel by 55% and 47%.(ABSTRACT TRUNCATED AT 250 WORDS)

Filtration characteristics of the single isolated perfused glomerulus of Myxine glutinosa.

Using an in vitro microperfusion technique, the filtration characteristics of single isolated glomeruli of the Atlantic hagfish (Myxine glutinosa) were investigated. The suitability of the method as a model to study glomerular function was evaluated. Experiments with a protein-free perfusate led to a filtration coefficient Kf (0.189 +/- 0.181 nl x s-1 x mm Hg-1) that was in the same order of magnitude as determined in vitro for other vertebrates. Morphometric analysis on serial thin sections (1 microns) revealed a glomerular capillary surface (A) of 1.84 +/- 0.72 mm2. A linear relationship between glomerular diameter and A allowed the calculation of the hydraulic conductivity Lp (0.618 +/- 0.384 microliter x s-1 x mmHg-1 x cm-2). The data indicate that the isolated perfused glomerulus of M. glutinosa has filtration characteristics similar to higher vertebrates. The glomeruli of M. glutinosa, which in contrast to glomeruli of other animals are easy to dissect, are a suitable model for the study of glomerular filtration and permeability characteristics of vertebrates. An example of a possible application of the model is a study into the effects of adrenaline on glomerular filtration characteristics. Adrenaline led to increases in ultrafiltration pressure (PUF), single nephron glomerular filtration rate (SNGFR) and filtration fraction (FF); Kf remained unaffected.

Effects of alpha 1-adrenergic blockade on intrarenal hemodynamics in heart failure rats.

To investigate intrarenal hemodynamics and effects of alpha 1-adrenergic blockade on glomerular functions in congestive heart failure (CHF), micropuncture studies were performed before and after intravenous injection of terazosin (1 microgram/100 g body wt iv) in eight myocardial infarction (MI) and in nine sham-operated rats after intraperitoneal injection of Inactin (70 mg/kg). CHF was characterized by elevated left ventricular end-diastolic pressure and increased total heart weight. In CHF rats, single nephron glomerular filtration rate (SNGFR), single nephron plasma flow (SNPF), and ultrafiltration coefficient (Kf) were decreased compared with sham-operated rats (SNGFR, 21.9 +/- 1.6 vs. 39.2 +/- 2.9 nl.min-1.g-1, P less than 0.01; SNPF, 66.6 +/- 6.1 vs. 133.8 +/- 10.5 nl.min-1.g-1, P less than 0.01; Kf, 0.019 +/- 0.001 vs. 0.041 +/- 0.004 nl.s-1.mmHg-1.g-1, P less than 0.01). Single nephron filtration fraction (SNFF), glomerular pressure (Pg), and efferent arteriolar resistance (Re) were higher in the CHF-MI rats than in the sham-operated rats (SNFF, 33.4 +/- 1.3 vs. 27.7 +/- 1.0, P less than 0.05; Pg, 60.2 +/- 1.6 vs. 53.3 +/- 0.8 mmHg, P less than 0.01; Re, 3.92 +/- 0.66 vs. 1.62 +/- 0.15 x 10(10) dyn.s.cm-5.g, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Renal vasoconstriction caused by short-term cholesterol feeding is corrected by thromboxane antagonist or probucol.

Recent studies indicate that short-term cholesterol feeding causes vascular hyperreactivity and/or increased tone in certain vascular beds. The present study in rats examined the effect of 3 wk of cholesterol-supplemented diet (CSD) on renal hemodynamics. We tested the hypothesis that LDL oxidized in vivo is causally related to increased renal vascular tone by adding the antioxidant drug probucol to the CSD (CSD + P). Micropuncture of surface nephrons in the CSD rats demonstrated that single nephron glomerular filtration rate (SNGFR) and single nephron afferent plasma flow (QA) were markedly lower than in normal rats, whereas glomerular capillary pressure (PGC), afferent arteriolar resistance (RA), and single nephron filtration fraction (SNFF) were higher. In the CSD + P animals, almost all of these hemodynamic abnormalities were absent. TXB2 and PGE2 were increased in proximal tubule fluid and urine in the CSD rats, but normal in the CSD + P group. Infusion of a TXA2 receptor antagonist into the suprarenal aorta of CSD rats caused a rapid return to normal of RBF (renal blood flow), GFR (glomerular filtration rate), SNGFR, QA, RA, PGC, and Kf (ultrafiltration coefficient). Our observations demonstrate that cholesterol feeding leads to renal vasoconstriction, which appears to be mediated largely by increased TXA2 production. The fact that probucol prevented the hemodynamic abnormalities as well as the increased TX production is consistent with the hypothesis that LDL oxidized in vivo initiates events leading to TX mediated vasoconstriction.

Galactose feeding causes glomerular hyperperfusion: prevention by aldose reductase inhibition

Experimental dietary galactosemia is known to result in accumulation of the polyol, galactitol, via the aldose reductase metabolic pathway in a variety of tissues, including renal glomeruli. Because increased polyol accumulation also occurs in insulin-dependent diabetes mellitus (IDDM), in which marked renal glomerular hyperperfusion occurs, we have studied glomerular hemodynamics in rats with experimental galactosemia. Insulin deficiency and its accompanying metabolic disorders are not present in this experimental model. In additional groups of animals, aldose reductase inhibitors, either sorbinil or tolrestat, were added to the galactose diet. In all, five groups of rats were studied: regular diet, 50% galactose diet, regular diet plus sorbinil, 50% galactose diet plus sorbinil, and 50% galactose plus tolrestat. The diets were comparable in protein and salt, and the rats were pair fed. Micropuncture and whole kidney clearance measurements were carried out after 10-14 days on these diets. Compared with rats fed the regular diet, those fed with 50% galactose diet had significantly higher glomerular filtration rates, renal plasma flow, single-nephron glomerular filtration rates, and plasma flow (QA), whereas afferent vascular resistance (RA) was decreased. Addition of sorbinil or tolrestat to the high-galactose diet not only prevented renal hyperperfusion but RA and single-nephron filtration fraction (SNFF) were higher than in normal rats, and QA was lower. In addition, sorbinil administration to rats on the control diet caused significant decreases in single-nephron blood flow and the ultrafiltration coefficient and a rise in SNFF.(ABSTRACT TRUNCATED AT 250 WORDS)

Sorbinil prevents glomerular hyperperfusion in diabetic rats

The role of polyol pathway metabolism in glomerular hyperperfusion of insulin-dependent diabetes mellitus (IDDM) was studied in rats. Streptozotocin-induced diabetic rats were fed the aldose reductase inhibitor, sorbinil (8 mg/day). Untreated diabetic rats and normal rats served as controls. All groups were fed the same diet, rationed to 20 g/day. Micropuncture, plasma renin activity (PRA), and glomerular angiotensin II (ANG II)-receptor measurements were made 7-15 days after streptozotocin injection. Untreated diabetic rats had higher than normal single-nephron filtration rate (SNGFR), plasma flow (QA), and blood flow (SNBF), and reduced afferent resistance. Glomerular ANG II-receptor sites were markedly decreased. In diabetic rats fed sorbinil SNGFR, QA, and SNBF were all lower than in untreated diabetic rats, and indistinguishable from values in normal rats. However, single-nephron filtration fraction (SNFF) rose above normal. PRA, glomerular ANG II receptors, and blood glucose were not affected by sorbinil. In normal rats fed sorbinil, SNGFR, QA, and SNBF were not significantly different than in normal rats. Our observations are consistent with the view that polyol pathway metabolism plays a role in glomerular hyperperfusion in IDDM. Inhibition of aldose reductase increased vascular smooth muscle tone at pre- and probably postglomerular sites.

Glomerular dynamics and salt balance in pregnant rats with renal hypertension.

These studies were aimed at investigating whether chronic hypertension in pregnancy causes changes both in salt excretion (NaE) and in glomerular hemodynamics. Metabolic and renal micropuncture studies were performed in pregnant (P) and Virgin (V) Munich-Wistar rats with normal blood pressure (N) and two-kidney Goldblatt hypertension (H). Mean NaE was higher in PN than VN (2.7 vs. 1.7 meq/day, P less than 0.01). Hypertension raised NaE both in P and V rats: in P and V rats with "benign" hypertension (blood pressure less than 180 mmHg) NaE averaged 3.2 and 2.6 meq/day, respectively (P less than 0.05); mean NaE was 5.9 and 3.8 meq/day, respectively (P less than 0.01), in P and V rats with "malignant" hypertension (blood pressure greater than or equal to 180 mmHg). Afferent arteriole resistance (Ra) averaged 1.73 and 3.50 10 dyn.s-1.cm5 in PN and VN, respectively (P less than 0.01). Hypertension raised Ra in V, but not in P rats (4.47 vs. 2.14 10 dyn.s-1.cm5, P less than 0.01). Thus glomerular plasma flow, glomerular capillary hydrostatic pressure, and single-nephron glomerular filtration rate were markedly higher in PH than VH rats: in PH rats single-nephron filtration fraction was significantly lower than in VH. These results show that in PH rats a marked rise in NaE is associated with glomerular vasodilation.

Vasoregulatory hormones and the hyperfiltration of diabetes

The role of renal vasoregulatory hormones in the hyperfiltration of early insulin-dependent diabetes mellitus (IDDM) was studied by micropuncture methods in rats with streptozotocin-induced diabetes. Seven to ten days after streptozotocin injection, untreated diabetic rats had elevated glomerular filtration rate (GFR) and single-nephron glomerular filtration rate (SNGFR), compared with normal euvolemic rats. Infusion of indomethacin (5 mg/kg) markedly reduced urinary and proximal tubular fluid prostaglandin E2 (PGE2), but GFR and SNGFR did not change. In a second group, intrarenal infusion of aprotinin (1,000 kallikrein inhibitor units.min-1.kg-1) to inhibit kallikrein also had no effect on GFR or SNGFR. In a third group, intrarenal infusion of angiotensin II (ANG II, 0.1 microgram.min-1.kg-1) reduced GFR, renal plasma flow (RPF), SNGFR, and glomerular plasma flow rate (QA) to values close to those in normal euvolemic rats. Single-nephron filtration fraction rose significantly with ANG II, but glomerular pressure (PG) was unaltered. Tubular fluid PGE2 increased in response to ANG II. Saralasin infusion following ANG II returned GFR, RPF, SNGFR, and QA to supernormal levels, and PG fell. In chronically salt-loaded normal rats, the responses to intrarenal ANG II and saralasin were similar to those observed in the diabetic rats. We conclude that hyperfiltration in early IDDM is not dependent on intact renal PGE2 or bradykinin synthesis. The results with ANG II infusion indicate that pre- and postglomerular and glomerular contractile cells of the diabetic kidney are able to constrict in response to this hormone.

Role of angiotensin II in the altered renal function of congestive heart failure.

Glomerular and tubule functions were assessed by micropuncture in rats with extensive myocardial infarction produced by ligation of the left coronary artery 4 weeks prior to study. When compared to sham-operated control rats, rats with myocardial infarction involving 40 +/- 4% of the left ventricular circumference had lower mean arterial pressure (96 +/- 5 vs. 122 +/- 4 mm Hg, P less than 0.005), and higher left ventricular end-diastolic pressure (24 +/- 3 vs. 5 +/- 0 mm Hg, P less than 0.001). Renal cortical microcirculatory dynamics of rats with myocardial infarction were characterized by reduced glomerular plasma flow rate (75 +/- 8 vs. 165 +/- 17 nl/min, P less than 0.005), but a proportionately lesser decline in single nephron glomerular filtration rate (28.0 +/- 2.8 vs. 41.7 +/- 3.1 nl/min, P less than 0.025), accounting for the observed rise in single nephron filtration fraction (0.38 +/- 0.02 vs. 0.25 +/- 0.02, P less than 0.005). These renal hemodynamic alterations in myocardial-infarcted rats were accompanied by a striking elevation in efferent arteriolar resistance (3.03 +/- 0.31 vs. 0.95 +/- 0.16 X 10(10) dyn X sec X cm-5, P less than 0.001). In addition, fractional proximal fluid reabsorption, assessed by end-proximal tubule fluid-to-plasma inulin concentration ratio, was elevated (2.21 +/- 0.12 vs. 1.64 +/- 0.09, P less than 0.025). The intravenous infusion of teprotide, an angiotensin I-converting enzyme inhibitor, led to the return of glomerular plasma flow rate, single nephron filtration fraction, single nephron glomerular filtration rate, efferent arteriolar resistance, and fractional proximal fluid reabsorption in myocardial-infarcted rats to, or toward, the levels found in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the micropuncture determination of single nephron filtration fraction

AbstractEvaluation of the micropuncture determination of single nephron filtration fraction. Spontaneous and aspirated blood samples were collected from the welling points of surface efferent arterioles in the rat kidney. The amount of tubular reabsorbate in each sample was calculated from measurements of the inulin concentration in the sample and systemic arterial plasma. Both spontaneous and aspirated samples contained substantial amounts of tubular reabsorbate (4% ± 1% and 11% ± 1%, respectively). Accordingly, the single nephron filtration fraction values derived from measurements of albumin concentrations alone were significantly lower than those calculated considering the addition of the amount of tubular reabsorbate in each sample (0.26 ± 0.01 vs. 0.30 ± 0.01 and 0.25 ± 0.01 vs. 0.34 ± 0.01 for the spontaneous and aspirated samples, respectively). Increasing the rate of blood collection from the welling point by aspiration was associated with a significant decrease in the hydraulic pressure in the same vessel. The efferent arteriolar blood samples were therefore probably contaminated with tubular reabsorbate as a result of retrograde flow from the peritubular capillaries. It was confirmed that single nephron filtration fractions derived from hematocrit measurements were significantly higher than those based on albumin concentration measurements, supporting that the hematocrit of afferent arteriolar blood of the superficial nephrons is higher than that of systemic arterial blood.Evaluation de la détermination par microponction de la fraction de filtration néphronique individuelle. Des échantillons de sang spontanés ou par aspiration ont été collectés à partir de points d'émergence d'artérioles efférentes superficielles dans du rein de rat. La quantité de réabsorbat tubulaire dans chaque échantillon a été calculée à partir de mesures de la concentration d'inuline dans l'échantillon et le plasma artériel systémique. Les échantillons spontanés et aspirés contenaient des quantités substantielles de réabsorbat tubulaire (4% ± 1% et 11% ± 1%, respectivement). De la sorte, les valeurs de fraction de filtration néphronique individuelle obtenues à partir des seules mesures de concentrations d'albumine étaient significativement plus faibles que celles calculées en prenant en compte en plus la quantité de réabsorbat tubulaire dans chaque échantillon (0,26 ± 0,01 contre 0,30 ± 0,01 et 0,25 ± 0,01 contre 0,34 ± 0,01 dans les échantillons spontanés et aspirés, respectivement). L'augmentation du débit de collection sanguin à partir du point d'émergence par aspiration était associée à une diminution significative de la pression hydraulique dans le même vaisseau. Les échantillons sanguins artériolaires efférents étaient de la sorte probablement contaminés avec du réabsorbat tubulaire résultant d'un flux rétrograde à partir des capillaires péritubulaires. Il a été confirmé que les fractions de filtration néphronique individuelle obtenues avec des mesures de l'hématocrite étaient significativement plus fortes que celles reposant sur des mesures de concentration d'albumine, ce qui indique que l'hématocrite du sang artériolaire afférent des néphrons superficiels est plus élevé que celui du sang artériel systémique.

Internephron heterogeneity of filtration fraction and disparity between protein- and hematocrit-derived values

The variability of single nephron filtration fraction (SNFF) and the relationship between filtration fractions determined simultaneously from 125I albumin (SNFFALB) and hematocrit (SNFFHCT) values were assessed by multiple samplings, 5 to 8 per kidney, in normal, hydropenic, Munich-Wistar rats. Single nephron filtration rate (SNGFR) measurements served as an independent marker of internephron heterogeneity. Whether derived as SNFFALB or SNFFHCT, a wide degree of internephron variability in SNFF, comparable to that found for SNGFR (P greater than 0.2) was observed in all kidneys. Hematocrit-derived SNFF values, however, were some 80% higher than those obtained with 125I albumin (SNFFHCT 0.447 +/- SEM 0.016 versus SNFFALB 0.258 +/- 0.009, P less than 0.001). The disparity in results obtained by the two methods disappears if the efferent arteriolar hematocrit (Hctg) is assigned a value 17 +/- SEM 1.4% higher than the corresponding femoral arterial hematocrit and might well be a reflection of the perfusion of superficial glomeruli with erythrocyte rich blood produced by the "plasma-skimming" phenomenon. The data suggest that multiple estimates of SNGFR and SNFF in a given rat kidney are needed to provide representative mean values for glomerular dynamic studies.

The existence of a tubulo-glomerular feedback mechanism in the Amphiuma nephron.

A single nephron tubulo-glomerular feedback control of the glomerular filtration rate, which is known in mammalian animals, could be one way by which amphibians regulate the glomerular filtration rate (GFR). To investigate whether the Amphiuma means shows any sign of a tubulo-glomerular feedback control, micropuncture experiments were carried out. Six different series of experiments were performed. In the first series, tubular stop-flow pressure (SFP) was measured during distal tubular perfusion with amphibian Ringer solution at a rate of 10, 25 and 50 nl/min. A significant decrease of SFP was found at the three perfusion rates compared to the controls. In the second group, single nephron glomerular filtration rate (SNGFR) was measured, while the distal tubule was perfused at 10, 25 and 50 nl/min. At a perfusion rate of 10 nl/min the SNGFR did not decrease, whereas at 25 and 50 nl/min it decreased significantly. In the third group the perfusion pipette was located in the proximal tubule and the nephron was perfused at 10, 25 and 50 nl/min, while at the same time the proximal tubular stop-flow pressure was measured. No reduction of SFP was found at a perfusion rate of 10 nl/min, while significant reductions were noted at rates of 25 and 50 nl/min. In the fourth group the SNGFR was measured in the distal tubule beyond the macula densa and in Bowman's space of the same nephron. No significant difference was found. In the fifth group, the glomerular capillary pressure (GCP) was measured before and after blockade of the tubular fluid flow. No significant difference was found between these two measurements. The sixth series deals with the changes occurring at the single nephron level by the tubulo-glomerular feedback control. The single nephron filtration fraction (FF) was determined from efferent arteriolar protein concentration with and without a feedback-induced reduction of the SNGFR. The FF values were not significantly different from one another. From these results and data from the other series, the afferent (Raff) and efferent (Reff) arteriolar resistances were calculated. Reff did not change, while Raff increased significantly when a feedback stimulus was applied. These experiments indicate the existence of a tubulo-glomerular feedback control which depresses the SNGFR and SFP by contracting the afferent arteriole.

Hemodynamic and single nephron function during the maintenance phase of ischemic acute renal failure in the dog

We studied ischemic acute renal failure in 28 dogs by micropuncture, microsphere, morphologic, and whole kidney hemodynamic techniques, 18 to 24 hours after the renal artery was clamped (clamping time, 60 to 90 min). Before the artery was clamped, renal blood flow (RBF) averaged 3.49 +/- (SEM) 0.23 ml/min x g and was not significantly different (3.70 +/- 0.34 ml/min x g) 18 hours after the ischemic episode. RBF autoregulatory capability was, however, significantly reduced. Fractional outer cortical blood flow decreased slightly from 41 +/- 2 to 36 +/- 3% (P less than 0.05) postischemia. Single nephron glomerular filtration rate (SNGFR) was highly variable from one animal to the next and ranged from 0 to 87 nl/min (mean, 36 +/- [SEM] 7 nl/min) in a manner similar to whole kidney inulin clearance, which ranged from 0 to 0.56 ml/min x g (mean, 0.30 +/- 0.05 ml+min x g). The correlation coefficient between SNGFR and inulin clearance was highly significant, indicating an association between SNGFR and whole kidney GFR. Proximal tubule pressure (PTP) averaged 20 +/- (SEM) 1 mm Hg. In 6 dogs, the glomerular filtration coefficient (Kf) was determined by measurements of stop-flow pressure, colloid osmotic pressure, SNGFR, PTP, and single nephron filtration fraction, Kf was below that obtained for control animals. Scanning electron microscopy (SEM) studies indicated that the endothelial fenestrations were reduced in number and size. These studies suggest that one major characteristic of ischemic nephropathy in the dog is a derangement in the filtration process. The maintenance of RBF in the postischemic phase may occur by utilization of the autoregulatory reserve of the renal vasculature.

Comparison of directly measured and calculated glomerular capillary pressure in the dog kidney at varying perfusion pressure.

To gain access to glomeruli of the dog kidney, an approximately 0.3 mm thick superficial tissue layer was cut off from the convexity of the kidney. The surface was superfused with warm Ringer's. Renal perfusion pressure (PP) was changed by an aortic clamp. The afferent oncotic pressure (pi A) was calculated from arterial plasma protein concentration, the efferent (pi E) from pi A and single nephron filtration fraction. At PP 17 and 13kPa, directly measured GCP was significantly lower than that calculated from stop-flow pressure (SFP + pi A). At PP8kPa, the difference was not significant. Hydraulic pressure differences across the glomerular capillary wall was still significantly different from pi E at PP 17 and 13 kPa. Hence, filtration pressure equilibrium was achieved in the dog kidney only at PP 8kPa.

Glomerular hemodynamics before and after release of 24-hour bilateral ureteral obstruction

Glomerular hemodynamics were studied, by micropuncture, in Munich-Wistar rats submitted to 24-hour bilateral ureteral ligation (BUL). Glomerular capillary pressure (PG), intratubular pressure (PT), and pressure in the first order peritubular capillaries (EAP) were measured with a servonulling device. Single nephron filtration fraction (SNFF) was calculated from arterial and peritubular blood protein concentrations. Single nephron glomerular filtration rate (SNGFR) was both measured by conventional micropuncture techniques and calculated from efferent arteriole blood flow and SNFF. Afferent arteriole blood flow (AABF) and resistance of afferent (Ra) and efferent (Re) arteriole were calculated. Measurements were repeated in the left kidney after releasing the ureter. Sham operated rats were used as control. BUL caused a fall in SNGFR (from 101.8 +/- 9.7 to 40.7 +/- [SEM] 6.0 nl/min/kg body wt), accounted for by a rise in PT (from 14.1 +/- 0.7 to 28.9 +/- 3.1 mm Hg), glomerular hemodynamics (particularly PG and AABF) being unchanged. A marked increase in Ra (from 6.6 +/- 0.7 to 10.8 +/- 1.5 dynes. sec. cm-5) occurred after releasing the ureter, lessening both PG and AABF. Therefore, a low SNGFR was maintained despite the concomitant normalization of PT.

Goldblatt hypertension in rats: a model for unilateral renal artery stenosis in man.

Determinants of glomerular ultrafiltration were studied by micropuncture in clamped (n = 11) and unclamped (n = 7) kidneys of two-kidney hypertensive rats and compared to 15 controls. Infusion of the angiotensin II antagonist and saralasin lowered the blood pressure significantly. Glomerular capillary pressure (PGC) in clamped kidneys was decreased to 56 +/- (SD) 3 vs. 61 +/- 3 mm Hg in controls. Early proximal flow rate (EPFR) was decreased to 20 +/- 1 vs. 26 +/- 2 nl/min in controls, at an unchanged single nephron filtration fraction (SNFF), indicating a reduced glomerular plasma flow (SNGPF). Preglomerular resistance (RA) was increased by 21%. In unclamped kidneys PGC was increased to 65 +/- 2 mm Hg. EPFR was increased to 32 +/- 2 nl/min, indicating, at an unchanged SNFF, an increased SNGPF. RA increased by 51%, whereas postglomerular resistance declined by 25%. The ultrafiltration coefficient was reduced by 24% in unclamped kidneys. Our results indicate that in clamped kidneys an increase of RA causes a reduction of PGC and hence a reduction of pressure at the baroreceptor site which may act as a trigger mechanism for renin release.

Effects of 24-hour unilateral ureteral obstruction on glomerular hemodynamics in rat kidney

Glomerular hemodynamics were studied, by micropuncture, in Munich-Wistar rats submitted to 24-hour unilateral ureteral ligation (UUL). Glomerular capillary pressure (PG), intratubular pressure (PT) and pressure in the first-order peritubular capillaries (EAP) were measured with a servonulling device. Single nephron filtration fraction (SNIFF) was calculated fmom arterial and peritubular blood protein concentration. SNGFR was both measured by conventional micropuncture techniques and calculated from efferent arteriole blood flow (EABF) and SNFF. Afferent arteriole blood flow (AABF) and resistance of afferent (Ra) and efferent (Re) arterioles were calculated. Measurements were repeated 1 to 2 hours after the release of the ureter. Sham-operated rats were used as control. UUL caused a marked increase in Ra (from 4.9 +/- [SD] 2.4 to 12.7 +/- 5.1 dynes/sec/cm-5). The fall in SNGFR (from 111.9 +/- [SD] 23.9 to 34.4 +/- 23.1 nl/min/kg body wt) was secondary to a decrease in both PG and AABF. A further increase in Ra (16.0 +/- 6.7 dynes.sec.cm-5) occurred after releasing the ureter. SNGFR, however, was unaltered (33.7 +/- 16.6 nl/min/kg body wt) since PG decreased parallel to PT, but AABF did not significantly change. Conclusion. Ureteral obstruction determines, in 24 hours, a marked cortical ischemia that is not promptly reversed by ureteral release.

Extraction methods for the determination of regional renal blood flow.

To permit determinations of the single nephron filtration fraction at vavarious levels of the cortex of the rat kidney, methods for single glomerular blood flow measurements were evaluated. Simultaneous measurements of the medullary blood flow were made with the different test substances. Intra-aortic slug injections of radioactive microspheres, 86-rubidium and 131-I-antipyrine were given in rats. The two kidneys were clamped 10 s after the injection, the pedicles were ligated and the kidneys were removed and deep-frozen. A reference arterial blood sample was drawn continuously during the 10-second period. In another series microspheres and 131-I-albumin were injected. The radioactivity of tissue samples and reference blood samples was analysed and the blood flow of cortical and medullary regions was calculated. The microspheres gave a blood flow of 6.65 ul/mg in outer cortex, 8.15 in mid-cortex and 4.91 ul/mg in inner cortex. Corresponding values with rubidium were 4.32 ul/mg, 4.56 ul/mg and 3.86 ul/mg and with antipyrine 2.14 ul/mg, 2.28 ul/mg and 1.97 ul/mg. In the outer stripe of the outer medulla a blood flow of 1.65 ul/mg was obtained with rubidium, 1.08 ul/mg with antipyrine and 0.75 ul/mg with labelled albumin. The corresponding values in the inner stripe of the outer medulla were 1.04 ul/mg, 0.66 ul/mg and 1.01 ul/mg and in the inner medulla 1.04 ul/mg, 0.66 ul/mg and 1.23 ul/mg. It is concluded that the microsphere technique gives the most reliable results for determination of the glomerular blood flow, but that both antipyrine and rubidium - although giving too low values - reflect the distribution pattern of blood flow within the cortical region. Rubidium seems to measure the blood flow reliably in all parts of the medulla and labelled albumin in the inner stripe and in the inner medulla.