Decrease In Renal Plasma Flow Research Articles

KIDNEY FUNCTION IN NORMAL MAN DURING SHORT-TERM GROWTH HORMONE INFUSION

Kidney function was studied in 9 normal males before and during a 2 h growth hormone (GH) infusion of 50 ng/kg/min. The following variables were measured during each 20 min clearance period: glomerular filtration rate, GFR, effective renal plasma flow, RPF (steady state infusion technique with urinary collections using [125I]iothalamate and [131I]iodohippurate), and urinary albumin and beta2-microglobulin excretion rates (radioimmunoassays). The GH infusion resulted in a 10-fold increase in plasma GH concentration. All the above mentioned variables remained practically unchanged during the infusion except for a small (-5%) but significant decrease in renal plasma flow (P less than 0.01). Our negative results contrast to the findings of increased GFR and RPF during prolonged GH administration and suggest that GH requires several hours or days for its renal effects to become manifest.

Changes in renal function in essential hypertension

Studies of renal hemodynamics, plasma renin activity (PRA), plasma aldosterone, and water and sodium excretion were performed in 171 patients with essential hypertension and 61 normotensive subjects. The para-amino hippurate clearance (C PAH) was usually normal or moderately reduced in those with benign hypertension and markedly depressed in those with malignant hypertension. The PAH extraction ratio was normal or slightly reduced in the patients with benign hypertension and moderately impaired in those with low C PAH indicating that a disproportionate decrease in cortical flow occurred only in the latter. The c pah did not correlate Inversely with the mean blood pressure in the patients with benign hypotension. Reexamination of untreated patients after an average of 28 1 2 months revealed a decrease in renal plasma flow but no further increase in blood pressure. These findings suggest that in uncomplicated hypertension the increase in blood pressure is not caused by renal circulatory disturbances. PRA was unrelated to renal hemodynamics in benign hypertension. In malignant hypertension, it was inversely correlated with the renal plasma flow. Under mild loading with isotonic saline solution, the fractional water excretion correlated with the blood pressure. Sodium excretion was neither related to the blood pressure nor to the estimated peritubular oncotic pressure, but correlated inversely with plasma aldosterone. These observations provide no support for the causative role of a primary disturbance in sodium excretion in essential hypertension.

REGULATION OF RENIN RELEASE AND INTRARENAL FORMATION OF ANGIOTENSIN. STUDIES IN THE ISOLATED PERFUSED RAT KIDNEY

1. Isolated rat kidneys were perfused at a constant pressure of 90 mmHg in a single-pass system with either a cell-free medium or a suspension of washed bovine red blood cells, free of the components of the renin-angiotensin system. In red blood cell perfused kidneys renal haemodynamics and sodium reabsorption corresponded closer to values observed in the intact rat than in cell-free perfused kidneys. 2. In red blood cell-perfused kidneys in the absence of plasma renin substrate autoregulation of renal blood flow was almost complete at pressures above 90 mmHg, provided that perfusion pressure was changed rapidly. 3. Renin release varied inversely with perfusion pressure within a pressure range from 50 to 150 mmHg; the greatest changes of renin release occurred, when perfusion pressure was reduced from 90 to 70 mmHg; maximal stimulation of renin release was observed at 50 mmHg. After reduction of perfusion pressure, renin release immediately started to rise and reached a new level within 5 min. Local reduction of perfusion pressure in small arteries and arterioles by the injection of microspheres induced a short-lasting decrease in renal plasma flow and a transient stimulation of renin release. 4. High concentrations of furosemide stimulated renin release by a direct intrarenal mechanism. 5. Isoproterenol stimulated renin release in low concentrations without a concomitant vasodilation, whereas high concentrations induced an increase in both renal plasma flow and renin release. The effects of isoproterenol were completely blocked by propranolol. 6. Sodium nitroprusside induced similar increases in renal plasma flow, as did high concentrations of isoproterenol, but only a small and slow increase in renin release was observed. 7. Angiotensin II (AII) suppressed renin release in concentrations corresponding to plasma levels measured in the intact rat independently of its vasoconstrictor effects, whereas vasopressin in antidiuretic concentrations did not affect renin release. 8. AII, AI, synthetic tetradecapeptide renin substrate (TDP), crude and purified rat plasma renin substrate induced a dose-dependent reduction in renal plasma flow. SQ 20 881, a competitive inhibitor of converting enzyme, and low doses of 1-Sar-8-Ala-AII (saralasin), a competitive antagonist of AII, did not change renal plasma flow, whereas high concentrations of saralasin had a vasoconstrictor effect on their own. 9. Saralasin inhibited the vasoconstrictor effects of AII and TDP to a similar degree. SQ 20 881 inhibited the vasoconstrictor effects of AI and purified renin substrate, but did not influence the actions of TDP and the crude renin substrate preparation. 10. From these data it is concluded, that AI is converted into AII within the kidney at a rate of 1-2%. The vasoconstriction induced by the crude renin substrate probably does not involve the AII receptors. TDP may act by itself on the AII receptors or via the direct intrarenal formation of AII...

Renal hemodynamics in respiratory acidosis--effects of hexamethonium bromide.

In 14 anesthetized dogs (control group) and 7 anesthetized dogs treated by Hexamethonium bromide (Hexa group), arterial carbondioxide tension (PaCO2), blood pH; renal plasma flow (RPF), renal blood flow (RBF), glomerular filtration rate (GFR), renal blood pressure (RBP) and renal vascular resistence (RVR) were measured before and during inhalation of 5% and 15% CO2. Cardiac output was observed in the control group. In the control group, moderate respiratory acidosis caused vasodilatation as evedenced by increase in RPF, . RBF and GFR, and a decrease of RVR. Severe respiratory acidosis caused vasoconstriction as evidenced by decrease in RPF, RBF and GFR, and an increase of RVR. Cardiac output remained relatively unchanged during CO2 inhalation. In the Hexa group, inhalation of 5% CO2 caused increase in RPF, RBF and GFR and a decrease of RVR. Hexamethonium bromide did not block renovascular dilatation in such a moderate respiratory acidosis. Inhalation of 15% CO2 in this group produced marked increases in RPF and RBF, and decreases in GFR and RVR; renovascular constriction observed in the control group was abolished by hexamethonium bromide. This observation confirms positive participation of sympathoadrenal mechanisms in regulation of renovascular responses and renal functions in respiratory acidosis.

Effects of intravenous diazoxide and chlorpropamide on renal function in man

The effects of 300 mg. of intravenous diazoxide and 1,000 mg. of intravenous chlorpropamide administered alone and in combination have been studied on specific renal functions in patients with pituitary diabetes insipidus and in a representative patient with essential hypertension during maximal sustained water diuresis as well as in hydropenia during osmotic diuresis produced by the infusion of hypertonic saline. During water diuresis in response to diazoxide within the first 10 to 20 minute urine flow, osmolal clearance and free water clearance increased. This transitory diuretic and natriuretic phase was followed by a marked antidiuresis and antinatriuresis. During water diuresis in the first hour of the study parallel with the decrease in renal plasma flow and glomerular filtration rate a marked reduction in urine flow and sodium excretion occurred. In the second hour antidiuresis and antinatriuresis continued but glomerular filtration rate and renal plasma flow began to approach the initial level. A close correlation was found between the reductions of osmolal and free water clearances both in absolute values and in values expressed in the percentage of GFR, suggesting increased sodium reabsorption in the proximal tubules. During osmotic diuresis diazoxide produced a marked antidiuresis and antinatriuresis apparently of both glomerular and proximal tubular origin, during the whole two hour study, with the exception of the slightly increased urine flow and osmolal clearance per nephron in the first 20 minutes. In patients with diabetes insipidus during the diazoxide induced “proximal type” antidiuresis, there was a parallel decrease in osmolal and free water clearances, whereas during the chlorpropamide induced vasopressin-like “distal type” antidiuresis free water clearance fell 70 per cent without any change in osmolal clearance. Only in the hypertensive patient in response to diazoxide the free water excretion was turned into free water reabsorption, demonstrating that mobilization of ADH may be also involved (as a third mechanism) in the diazoxide induced antidiuresis.

Effects of dextran on postoperative renal function measured by a single injection clearance method.

Effects of dextran infusion on postoperative renal function were studied by determination of the glomerular filtration rate with 135I-iothalamate and effective renal plasma flow with 131I-hippuran clearance, using a single injection technique. After cholecystectomy a decrease in renal plasma flow was observed in control patients. Infusion of dextran during the operauon did not abolish this decrease in renal plasma flow. The glomerular filtration rate was fairly constant in both groups of patients. According to the present results, dextran infusion during the performance of a standard abdominal operation does not offer any advantage over the use of crystalloid solutions from the point of view of renal function.

Investigation of nephrotoxic effects of adenine and its metabolic product, 2,8-dioxyadenine, on primates (Macaca irus).

Abstract : Primates injected with one 10 mg/kg dose of adenine over 10 min or the same dose daily for 5 days had no changes in renal function or structure. Single doses of 25 or 50 mg/kg produced decreases in renal plasma flow and/or glomerular filtration which appeared to be dose related. No crystalline deposition or pathological changes were observed in the renal tissue at any dose level. Transient crystalluria was observed in some animals at the time of urinary adenine and 2,8-dioxyadenine excretion, but these crystals were not definitely identified. Adenine and 2,8-dioxyadenine were present in the urine at all dose levels during the first day, but were absent 24 hr after injection. (Author)

Continuous recording of renal isotope clearance by external monitoring during general anesthesia.

In 7 patients undergoing general anesthesia and transurethral resection of the prostate, the effective renal plasma flow (ERPF) was recorded before, during and after anesthesia using a new isotope feedback technique. The isotope we used was I131 iodopyracet. In comparison to the average preanesthetic I131 iodopyracet clearance (319 ml/min), the clearance measurements during general anesthesia in 7 patients revealed a fall in ERPF of 32%. In 5 of these patients receiving pentothal-N2O-oxygen anesthesia there was a decrease of renal plasma flow of 30%. Epidural anesthesia was attempted in the remaining two patients but proved to be insufficient. One of these patients received nitrous oxide-oxygen anesthesia which caused a fall in ERPF of 31%. To the second patient halothane-N2O-oxygen anesthesia was given, which was followed by a decrease in renal plasma flow of 44%. A more detailed study revealed a fall of 29% in iodopyracet clearance during general anesthesia before operation and a fall of 35% during transurethral prostatectomy. After general anesthesia we found in all patients a marked increase of renal plasma flow.

Intrarenal control of proximal tubular reabsorption of sodium and water.

The effect of variations in the rate of peritubular capillary removal of tubular epithelial reabsorbate on net reabsorption of fluid from the proximal tubule was studied in rat kidneys by micropuncture techniques. Elevation of the renal venous pressure induced by partial occlusion of the renal vein resulted in decreased proximal tubular reabsorption. This reduction was proportional to the decrease in renal plasma flow. During control conditions an inverse linear relationship was observed between filtration fraction (CIn/Cpah) and the half time of fluid reabsorption, suggesting that an increase in the oncotic pressure in peritubular capillaries facilitates proximal tubular fluid reabsorption. Direct evidence for this hypothesis was obtained in free flow and split drop experiments in which the peritubular capillaries were perfused through micropipettes, with fluid of different oncotic pressures. When the capillary perfusate consisted of colloid-free Ringer’s proximal reabsorption was markedly depressed. AdditioC of 8 g/l00 ml of high molecular Dextran to Ringer’s restored tubular reabsorptive capacity to control levels. The results obtained in these studies demonstrate that a significant portion of tne overall net movement of fluid depends upon the rate of vascular removal of the epithelial reabsorbate.

Alterations in renal cortical blood flow in infants and children with urinary tract infections.

Extract: The present studies were designed to elucidate renal functional changes in infants and children with urinary tractinfections. Twenty-three infants and children ranging in age from 4 months 13 6/12 years with urinary tract infections were studied. Four children ranging in age from 2 to 6 10/12 years without documented urinary tract infections served as controls. Inulin clearances (CI) were utilized for measurement of golmerular filtration rate. Renal plasma flow and tubular maximum excretory capacity were ascertained by the intravenous administration of para-aminophippurate (PAH). Second determinations performed in eight patients and a third determination in one patient provided longitudinal follow-up. Renal plasma flow measurements were low in 4 of 6 infants and in 6 of 17 children on initial testing; these decreased values were associated with normal glomerular filtration rates except in 3 subjects. In the 4 patients without documented urinary tract infections. CPAH values were within the normal range. CPAH values obtained initially in all subjects were compared on a surface area basis to those chracteristic of normal children. Of the 27 experimental points, 21 were below the line representing the normal average CPAH for children. In this small series, only one of three infants failed to recover this function at the time of repeat testing. The recovery rate was less in the children studied. The data indicate that a decrease in renal plasma flow occurs prior to significant alterations in the other renal functional parameters measured. Twenty-two subjects were tested for both CPAH and TmPAH. The ratio (CPAH/TmPAH) was lower in all three groups than the reported normal value of 7.7. In those patients demonstrating an initially reduced value, 13 of 16 showed normal CPAH values. These findings could represent renal ischemia of proximal tubular tissue. The persistence of renal vascular changes in the face of absent clinical and/or laboratory evidence of urinary tract infections exmphasizes the need for caution in identifying the prognosis of children with pyelonephritis and the need for careful long-term evaluation. Speculation: Although it has been well documented that the renal medulla is the primary site of involvement in pyelonephritis, the current data suggest that the post-glomerular capillaries and tubular structures in the renal cortex are also early sites of invlovement in infants and children. A question raised by the study is the relation of reduced renal plasma flow measurements to the natural history and pathogenesis of recurrent pyelonephritis. It is suggested that agents promoting a change toward normal renal circulation may reverse the pathologic process.

Effects of salt loading and haemodilution on the responses of perfused cat kidneys to angiotensin

1. Effects of single intra-arterial injections (0.1-1.0 mug) of angiotensin II have been observed on cat kidneys perfused with heparinized blood from heart-lung circuits.2. Angiotensin II always caused an abrupt decrease in renal plasma flow (R.P.F.) which reached maximum in 1-2 min and lasted over-all for only 3.5-4.0 min. Glomerular filtration rate (G.F.R.) usually and filtration fraction (F.F.) always increased.3. Angiotensin II caused antidiuresis provided that the kidney had not been subjected either to salt loading or to haemodilution within the preceding 3 hr. These pretreatments converted the antidiuretic action of angiotensin into a diuresis.4. Angiotensin II raised the rate of Na excretion, the urinary concentration of Na and the urinary Na/K whether anti-diuretic or diuretic.

A case of villous adenoma of the rectum with hyperaldosteronism and unusual renal manifestations

A case of villous adenoma of the rectum with severe fecal loss of electrolytes and unusual renal manifestations is presented. Large quantities of sodium and potassium were lost in the feces; the resultant renal abnormalities were documented by renal function studies, which showed a decrease in renal plasma flow and renal conservation of sodium and potassium. Alkalosis usually was present rather than the acidosis characteristic of the syndrome, probably because of the loss of potassium with resultant loss of hydrogen ions into body cells or into the urine as ammonium. With hypovolemia, a reversible contraction of the kidneys, associated with impairment of renal tubular function, was shown on the urograms. Surgical removal of the villous tumor resulted in dramatic reversal of all clinical symptomatology and the eradication of all abnormalities of renal function and fluid balance.

Early effects of thyrotropin on PBI 131 release and on plasma iodide 131 disappearance

gm./day; phosphorus (+) 0.43, (+) 1.60 gm./ day; nitrogen 0.0 gm. and (-) 3.0 gm./day. On prednisone therapy the patients were in positive balance, 3 and 7 gm./day, respectively. During the twenty-one-day study the body weight loss was 4.0 and 5. 0 kg., respectively. Renal function tests, glomerular filtration rate (inulin, Cr), renal plasma flow, Tm (PAH) showed only a decrease in renal plasma flow of 18 and 35 per cent, as compared to measurements the day prior to administration of halogenated steroid. The levels of glucose and plasma electrolytes remained stable. Negative electrolyte balance is a major factor in weight loss. The clinical status of both patients was controlled throughout the study.

Uretero-renal reflex facilitating renal vasoconstrictor responses to emotional stress.

In trained and conscious dogs, with ureters exteriorized in flank skin-flaps to facilitate the simultaneous determination of unilateral renal function, it was determined that unilateral irritation of the ureter reflexly produced a decrease in renal plasma flow and glomerular filtration rate in the ipsilateral kidney. Three unilateral renal response patterns were observed on catheterizing the ureter. This uretero-renal reflex was always unilateral and ipsilateral with respect to the stimulated ureter, and could be blocked by anesthetizing the ureter, denervating and/or transplanting the kidney. It was determined that sensory fibers from the ureter communicate reflexly with renal efferent vasoconstrictor fibers. These ureteral afferent fibers pass up the entire length of the ureter where they probably enter the splanchnic nerves. Afferent discharges from the stimulated ureter, whether acute or subliminal, selectively promoting the recruitment of preganglionic neurons, effectively facilitate renal nerve pathways to the kidney under conditions of sympathetic activation (stress). It was concluded that the mechanism of action of this uretero-renal (viscero-visceral) reflex, and its functional significance to renal vasomotor regulation, is that of a facilitating phenomenon. By this facilitating action it channelizes sympathetic activity into efferent renal nerve pathways, exposing the kidney to an exaggerated impact from general and nonspecific environmental stress factors.

Effects of magnesium sulfate on renal function, electrolyte excretion and clearance of magnesium.

The constant intravenous infusion of magnesium sulfate in patients with chronic renal disease produced a significant decrease in renal plasma flow, no change in glomerular filtration rate and no alteration in urinary excretion of sodium, chloride and potassium. Normal men had shown a similar decline in renal plasma flow but also a decrease in glomerular filtration rate, an increase in urinary excretion of sodium and chloride and a decrease in urinary excretion of potassium. The serum concentrations of these electrolytes were not altered in either group. The values for clearance of magnesium in this study were below those required to implicate tubular excretion of this ion. Submitted on October 15, 1956

Mechanism of early and chronic experimental renal hypertension as tested by CCK-179.

The effects on blood pressure and renal clearances of a combination of dihydrogenated ergot alkaloids, CCK-179, were studied in normal dogs and dogs with experimental renal (Goldblatt) hypertension. The drug was observed to have a maximal effect at 0.012 mg/kg, about one twelfth to one sixteenth the dose recommended in the literature. In normal dogs the drug causes a slight fall in blood pressure, a moderate decrease in glomerular filtration rate (creatinine clearance) and a pronounced decrease in renal plasma flow (PAH clearance), hemodynamic effects resembling those seen in man. After repeated administration of the drug, the renal effects are of greater magnitude in these dogs. In hypertensive dogs, CCK-179 causes blood pressure to approach normal levels. In the early weeks of hypertension, the renal effects of the drug are similar to those seen in normals but as hypertension increases in duration up to 55 weeks, the decreases in filtration rate and plasma flow become progressively smaller. This could indicate that in chronic experimental renal hypertension the high peripheral resistance is maintained at least in part by increased activity of the sympathetic nervous system rather than by the action of the components of the renal humoral pressor system.

CLINICAL OBSERVATION OF DIABETES INSIPIDUS (Ist REPORT)

Water and electrolyte metabolism was studied in 25 cases with diabetes insipidus, and the following results were obtained:(1) Daily urinary volume in most of the cases (88%) did not exceed eight liters.(2) In the dilution and concentration test, their dilution capacity was not impaired, however, the urinary output per unit of hour was rather uniform, which was indicative of primary polyuria. On the contrary, there were variable degrees of severe impairment of their concentrating capacity.(3) Renal blood flow (RBF), renal plasma flow (RPF), glomerular filtration rate (GFR) and filtration fraction (FF) were not significantly different from those of normal subjects, whereas tubular reabsorption rate (TRR) was materially reduced (10 cases).(4) There was somewhat increased excretion rate of PSP (5 cases).(5) Serum antidiuretic substance (ADS) was at the lower range of that of normal in 6 out of 7 cases. There was also no daily or diurnal variation of ADS, and no decrease was observed following the water load by mouth.(6) By intravenous infusion of hypertonic saline solution, there was a slight decrease in urinary output in one of 4 cases, whereas there was a slight or moderate increase in urinary output in the rest of the cases without elevation of urinary and plasma chloride concentration ratio.(7) By intravenous administration of 0.8 to 2.0mg of nicotine, there was a slight decrease in urinary output in one of 3 cases, whereas no decrease in the rest of the cases.(8) There was no demonstrable change in serum electrolyte concentration (11 cases); there was, however, a marked increase in K/Ca as a result of increased serum potassium concentration following posterior pituitary transplantation.(9) Daily urinary output significantly decreased after posterior pituiatry transplantation, which was accompanied by increase in serum ADS, abolition of urinary dilution capacity and prolongation of time required for disappearance of the elevation produced by intradermally injected salt solution by method of McClure and Aldrich (2 cases). A slight decrease in RPF with increase in GFR, resulting in increase of FF, and elevation of TRR were observed following the transplantation (1 case).