Factors affecting the maturation of renal PAH extraction in the new-born dog

1. The maturation of renal para-amino-hippurate extraction (E(PAH)) was studied in thirty-nine mongrel new-born dogs aged 2-29 days. E(PAH) was also measured in five adult dogs for comparison.2. There was no apparent change of PAH extraction during the first month of life but E(PAH) was lower in the puppy than in the adult. Under mannitol diuresis E(PAH) averaged 0.49 for the puppies and 0.83 for the adult dogs (P < 0.001). E(PAH) averaged 0.48 for the puppies under nondiuretic conditions, a value not significantly different from that observed during mannitol diuresis. There was no correlation of E(PAH) with mean arterial blood pressure.3. Inulin extraction (E(In)) remained constant during the first month of life and was the same in the new-born and adult dog suggesting that preglomerular shunting of plasma away from functioning nephrons was the same for both the puppy and adult dog.4. E(PAH) did not change in the puppy when plasma concentrations varied from trace (using [(3)H]PAH) to 0.25 mM indicating that excessive PAH load is not a factor in the low E(PAH) of the puppy.5. Diffusion of PAH from the red blood cell was excluded as an explanation for the low E(PAH) since diffusion was the same for both the adult and new-born dog.     

Intrarenal renin and autoregulation of renal plasma flow and glomerular filtration rate.

Autoregulatory responses of renal plasma flow (RPF) and glomerular filtration rate (GFR) to reductions in renal artery pressure (RAP) were studied in both kidneys of two-kidney, one-clamp dogs and in dogs treated with deoxycorticosterone acetate (DOCA; 25 mg/kg) plus high sodium diets with and without renal arterial clamping. In non-DOCA-treated animals, unilateral renal artery constriction resulted in a significant difference (P = 0.004) in renal renin activity (RRA) between the clamped (171 +/- 37 ng AI.mg-1.h-1) and the contralateral (57 +/- 23 mg AI.mg-1.h-1) kidneys with no change in their relative autoregulatory ability. In dogs treated with DOCA/high sodium there were no differences in RRA between the clamped and contralateral kidneys. The dogs treated with DOCA/high sodium were able to autoregulate both RPF and GFR even though their RRA was only 5.4 ng AI.mg-1.h-1. DOCA/high sodium treatment, however, reduced basal RPF (22%) and GFR (23%) below those in non-DOCA-treated animals. Analysis of the autoregulatory ability of individual kidneys showed no relationship to either RRA or renin secretory rates. These results support the conclusion that the renin-angiotensin system is not necessary component in the autoregulation of RPF or GFR.     

Angiotensin II and renal prostaglandin release in the dog. Interactions in controlling renal blood flow and glomerular filtration rate

The relationship between angiotensin II and renal prostaglandins, and their interactions in controlling renal blood flow (RBF) and glomerular filtration rate (GFR) were investigated in 18 anaesthetized dogs with acutely denervated kidneys. Intrarenal angiotensin II infusion increased renal PGE₂ release (veno-arterial concentration difference times renal plasma flow) from 1.7 ± 0.9 to 9.1 ±0.4 and 6-keto-PGFja release from 0.1 ±0.1 to 5.3 ± 2.1 pmol min^-1. An angiotensin II induced reduction in RBF of 20% did not measurably change GFR whereas a 30% reduction reduced GFR by 18 ± 8%. Blockade of prostaglandin synthesis approximately doubled the vasocon-strictory action of angiotensin II, and all reductions in RBF were accompanied by parallel reductions in GFR. When prostaglandin release was stimulated by infusion of arachidonic acid (46.8± 13.3 and 15.9± 5.4 pmol min^-1 for PGE₂, and 6-keto-PGFja, respectively), angiotensin II did not change prostaglandin release, but had similar effects on the relationship between RBF and GFR as during control. In an ureteral occlusion model with stopped glomerular filtration measurements of ureteral pressure and intrarenal venous pressure permitted calculations of afferent and efferent vascular resistances. Until RBF was reduced by 25–30% angiotensin II increased both afferent and efferent resistances almost equally, keeping the ureteral pressure constant. At greater reductions in RBF, afferent resistance increased more than the efferent leading to reductions in ureteral pressure. This pattern was not changed by blockade of prostaglandin synthesis indicating no influence of prostaglandins on the distribution of afferent and efferent vascular resistances during angiotensin II infusion. In this ureteral occlusion model glomerular effects of angiotensin II will not be detected, and it might well be that the shift from an effect predominantly on RBF to a combined effect on both RBF and GFR induced by inhibition of prostaglandin synthesis is located to the glomerulus. We therefore postulate that renal prostaglandins attenuate the effects of angiotensin II on glomerular surface area and the filtration barrier, and not on the afferent arterioles as previously suggested.     

Maturation of glomerular blood flow distribution in the new-born dog

1. Glomerular blood flow distribution was studied in seventy-eight new-born mongrel dogs aged 1-40 days by measuring the distribution of radioactive labelled microspheres within the kidney.2. The microsphere technique was found to be a valid indicator of glomerular blood flow distribution for the new-born dog since (a) the spheres were completely extracted by the kidney, (b) more than 95% of the spheres were trapped in glomerular capillaries, (c) the spheres were evenly distributed within any specific region of the kidney and, (d) the spheres did not interfere with renal haemodynamics.3. Plasma flow per gram tissue to inner cortical glomeruli, relative to that to outer cortical glomeruli, the IC/OC flow ratio, was high at birth, decreased over the first 2 weeks of life and remained relatively constant thereafter. Plasma flow per gram tissue to the outer cortex increased over the whole 40 day period while that to the inner cortex decreased slightly and then increased after 2 weeks.4. The IC/OC flow ratio decreased in a curvilinear fashion as blood pressure rose with maturation. Acute increases or decreases in blood pressure in any animal produced decreases or increases, respectively, in the IC/OC flow ratio.5. There was no correlation between the IC/OC flow ratio and renal extraction of p-amino-hippurate (E(PAH)).6. There was histological evidence that glomerular differentiation persists for 2 weeks during the post-natal period in the dog. This continuing post-natal glomerulogenesis takes place only in the outer cortex.7. These results are consistent with the hypothesis that an important factor in renal maturation is a redistribution of blood flow within the kidney. As the animal matures a greater fraction of the total glomerular blood flow goes to outer cortical glomeruli. This is due partly to the continuing glomerular differentiation taking place in the outer cortical region and partly to the increasing arterial blood pressure occurring with maturation.     

Redistribution of glomerular filtration and renal plasma flow in CNS-induced natriuresis

Infusion of hypertonic sodium chloride solution into the third cerebral ventricle results in a marked increase in renal sodium output, indicating an important regulator of extracellular volume homeostasis. The intrarenal events governing the enhanced excretion have not been thoroughly studied previously. In 12 anaesthetized male rats a stainless steel cannula was introduced stereotaxically into the right lateral cerebral ventricle. Urine volume and excretion rates, Na, K, and osmotically active particles were measured during control infusion of artificial cerebrospinal fluid and during stimulation of central mechanisms with I M NaCl (520 nl min-1). At the end of the stimulation period, regional renal plasma flow (86RbCl) and glomerular filtration rate (51Cr-EDTA) were measured with single injection techniques. A second group of 12 non-stimulated rats served as controls. During ICV stimulation, the urine flow rate increased from 1.8 +/- 0.19 to 6.4 +/- 1.01 microliter min-1 (P less than 0.001). The urinary concentrations of Na and K increased, leading to a rise in the excretion rates of these ions from 0.12 +/- 0.025 to 0.96 +/- 0.352 mumol min-1 (P less than 0.001) and 0.40 +/- 0.083 to 1.70 +/- 0.196 (P less than 0.001), respectively. The osmolar excretion rate was 2.9 +/- 0.35 mu Osm min-1 before stimulation and 9.6 +/- 1.09 higher (P less than 0.001) during stimulation. Simultaneously the inner medullary plasma flow rose two-fold from 0.7 +/- 0.06 to 1.4 +/- 0.12 microliter min-1 tissue (P less than 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)     

Two models of glomerular filtration rate and renal blood flow in the rat

Two mathematical models of glomerular filtration and blood flow are derived. The first is based on principles of fluid and mass conservation in individual capillaries. The model explains why the filtration rate (GFR) is strongly dependent on local hydrostatic and protein oncotic pressures, and on plasma flow rate (GCPF), but only weakly dependent on exact numbers, lengths, radii, or filtration coefficient of glomerular capillaries. The model shows that much of the increased GFR in both isooncotic plasma loading and isotonic Ringer's loading is due to increased GCPF caused by diluting erythrocytes. The second model uses several approximations and reduces to a quadratic in afferent arteriolar blood flow. When arterial pressure, hematocrit, plasma protein concentration, and afferent and efferent arteriolar resistances are specified, the model predicts GFR, afferent arteriolar blood flow, and filtration fraction. Alternatively, if any two of these three variables are known, the model predicts segmental arteriolar resistances. The model indicates that GFR and blood flow regulation must be located in the afferent arteriole, despite the strong dependence of GFR on GCPF.     

Measurement of renal plasma flow and glomerular filtration rates in diabetic subjects]

To clarify the problem in the measurement of renal plasma flow and glomerular filtration rates in diabetes, the effect of glucose on the determination of para-aminohippuric acid (PAH) and inulin was examined. The concentration of urinary PAH in glucosuric diabetic subjects decreased after the storage of urine samples because of the glycation of PAH. Therefore, glucose must be removed by the acid treatment before the determination of the concentrations of urinary PAH. Since glucose can interfere with the assay of inulin, the sample must be treated with NaOH prior to the determination of the inulin concentration. GFR of the subjects with type 2 diabetes was next examined. GFR in the subjects with a duration of diabetes less than 10 years was significantly higher than that in the subjects with a duration of diabetes more than 10 years. Thus, the subjects with short-term type 2 diabetes may present with hyperfiltration similar to the subjects with short-term type 1 diabetes.     

The renal blood flow and the glomerular filtration rate of anaesthetized dogs during acute changes in plasma sodium concentration.

1. The effects of acute changes in plasma Na concentration (P(Na)) on renal blood flow (RBF) and glomerular filtration rate (GFR) were studied in anaesthetized greyhounds. Saline was infused at a constant rate (0.1 ml. kg(-1) min(-1)) either into a renal artery or into a systemic vein. Plasma Na concentration was altered by varying the Na concentration of the infused saline from 0.154 to 0.077, 0.616 or 1.232 M.2. Blood pressure (B.P.), packed cell volume (PCV), concentration of plasma solids (PS) and the plasma concentration of H(+) and K (P(K)) ions were measured but no attempt was made to contain their fluctuation.3. An infusion of hypertonic saline into a renal artery usually led to an ipsilateral increase in RBF for 5-15 min, followed by a progressive fall. Over-all, mean values of RBF fell with P(Na) throughout the range studied (120-190 m-mole l.(-1)). Glomerular filtration rate rose with P(Na) to reach maximal values at P(Na) levels of 140-160 m-mole l.(-1), but fell thereafter. The combined fall in RBF and GFR, without change in filtration fraction, at P(Na) values above 160 m-mole l.(-1) is consistent with an alteration in afferent arteriolar resistance. The fall in GFR despite a rise in RBF noted when P(Na) was reduced below 140 m-mole l.(-1) requires an additional explanation.4. Renal blood flow was independent of P(K); it was inversely related to [H(+)] and directly related to PS. Glomerular filtration rate was independent of PCV and P(K). It was also inversely related to [H(+)] and directly related to PS up to a value of 6 g 100 g(-1) plasma, after which the relationship was reversed. These results suggest that the renal vascular responses to acute changes in P(Na) may be mediated in part, at least, by concurrent change in PS and [H(+)].     

Autoregulation of renal blood flow,glomerular filtration rate and renin release in conscious dogs

The relationship between renal artery pressure (RAP), renal blood flow (RBF), glomerular filtration rate (GFR) and the renal venous-arterial plasma renin activity difference (PRAD) was studied in 22 chronically instrumented, conscious foxhounds with a daily sodium intake of 6.6 mmol/kg. RAP was reduced in steps and maintained constant for 5 min using an inflatable renal artery cuff and a pressure control system.Between 160 and 81 mm Hg we observed a concomitant autoregulation of GFR and RBF with a high precision. The break off points for GRF- and RBF-autoregulation were sharp and were significantly different from each other (GFR: 80.5±3.5 mm Hg; RBF: 65.6±1.3 mm Hg;P<0.01). In the subautoregulatory range GFR and RBF decreased in a linerar fashion and ceased at 40 and 19 mm Hg, respectively.Between 160 mm Hg and 95 mm Hg (threshold pressure for renin release) PRAD remained unchanged; below threshold pressure PRAD increased steeply (average slope: 0.34 ng AI·ml^–1·h^–1· mm Hg^–1) indicating that resting renin release may be doubled by a fall of RAP by only 3 mm Hg. At the break-off point of RBF-autoregulation (66 mm Hg) renin release was 10-fold higher than the resting level.It is concluded that under physiological conditions (normal sodium diet) GFR and RBF are perfectly autoregulated over a wide pressure range. Renin release remains suppressed until RAP falls below a well defined threshold pressure slightly below the animal's resting systemic pressure. RBF is maintained at significantly lower pressures than GFR, indicating that autoregulation of RBF also involves postglomerular vessels. Our data are in agreement with the myogenic hypothesis as a basic mechanism of autoregulation.This study was supported by the German Research Foundation (FG Niere, Kr. 546/5-1, Projekt 3). A preliminary report of a part of this investigation has been presented to the Vth European Colloquium on Renal Physiology 1985 (Kirchheim et al., Renal Physiol, Basel 9:84, abstract 80, 1986)     

Changes in the rate of effective plasma flow,the rate of glomerular filtration,and the filtration fraction in the kidneys during serum sensitization

Summary Experiments were performed on 5 male dogs with ureteric orifices exteriorized into the abdominal skin. The author studied the effect of serum sensitization on the effective plasma flow (determined by means of cardiotrast), on the glomerular filtration (determined by inulin), and on the filtration in the kidneys. A reduction of cardiotrast clearance was noted in the majority of the experiments; inulin clearance was changed within limits approaching normal values; however, in individual cases it was markedly increased and as a rule the filtration fraction showed a rise.(Presented by Active Member AMN SSSR E. M. Tareev) Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny Vol. 49, No. 5, pp. 59–62, May, 1960     

Serotoninergic hepatorenal reflex regulating renal glomerular filtration rate

Summary Infusion of glutamine (2 mol/min) into the superior mesenteric vein leads to a decrease of renal glomerular filtration rate (GFR) and urinary flow rate (V), whereas infusion of identical amounts of glutamine into the jugular vein does not significantly alter GFR or V. The effect of mesenteric glutamine is mimicked by mesenteric infusion of 5 nmol/min serotonin and is abolished in the presence of 20 nmol/min methysergide. The effect of mesenteric serotonin is almost abolished after transection of vagal hepatic nerves. The observations point to a serotoninergic hepatorenal reflex regulating renal function.