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Biomedical subjects

M G Cogan

Publications and source records attributed to M G Cogan.

At least 55 records · Page 3Linked to original sources
PubMed1986

Effect of atrial natriuretic factor on acid-base homeostasis.

Both micropuncture and clearance studies have shown that the anion excreted in the urine in response to the increased glomerular filtration rate and solute load induced by atrial natriuretic factor (ANF) depends on the pre-existing acid-base status. In normal animals, the kidney is relatively better at reabsorbing bicarbonate than chloride, as ANF increases luminal flow so that a chloruresis without bicarbonaturia ensues. In contrast, during chronic hypochloraemic metabolic alkalosis, alkalaemia renders the kidney unable to reabsorb the increment in filtered bicarbonate induced by ANF so that bicarbonaturia occurs with amelioration of the alkalosis. Since the relative magnitudes of chloride versus bicarbonate excretion rates in response to ANF are a function of the plasma anion concentrations, ANF tends to correct acid-base disorders.

Acid-Base Equilibrium↗
PubMed1986

Renal hemodynamic and natriuretic effects of atrial natriuretic factor.

In this article we review the renal hemodynamic and excretory actions of atrial natriuretic factor (ANF) and consider some of the mechanisms of its vascular and natriuretic effects. ANF leads to a marked, sustained, and parallel increase in whole-organ and superficial single-nephron glomerular filtration rate (GFR) while mean blood pressure is decreased and renal blood flow (RBF) is unchanged or even decreased. The increase in GFR is caused by an efferent arteriolar vasoconstriction or by a combination of afferent vasodilation and efferent vasoconstriction. ANF also leads to a decrease in the hypertonicity of the innermedullary interstitium. Together with the increase in GFR, this phenomenon accounts wholly or in great part for the ANF-induced natriuresis. The overall renal vascular effects of ANF are complex and may tentatively be conceptualized as a behavior of a functional partial agonist: slight vasoconstriction in vasodilated kidneys, no sustained effects on the vascular resistance in normal kidneys, and vasodilation in vasoconstricted kidneys. The vasoconstrictor effect of ANF may be direct or indirect and depends on extracellular calcium whereas the antagonist effect likely results from alterations in intracellular calcium homeostasis. The data raise the perspective that ANF is not only a powerful natriuretic substance but has the potential of being an important modulator of GFR and RBF in intact animals.

Aldosterone↗
PubMed1985

Atrial natriuretic factor ameliorates chronic metabolic alkalosis by increasing glomerular filtration.

The kidney maintains the elevated plasma concentration of bicarbonate that occurs in chronic metabolic alkalosis. A reduction in the glomerular filtration rate (GFR) can maintain the filtered bicarbonate load at a normal level so that a normal rate of bicarbonate reabsorption suffices to prevent urinary excretion of this anion. It is also possible that bicarbonate reabsorption might increase so as to maintain the alkalosis if GFR were not reduced. To examine this latter possibility, atrial natriuretic factor was used in alkalotic rats to restore a more normal GFR and to increase the amount of bicarbonate filtered by the glomerulus. Proximal bicarbonate reabsorption remained relatively static. Higher than normal amounts of bicarbonate were then delivered out of the proximal tubule, bicarbonate appeared in the urine, and the plasma concentration of bicarbonate fell. A reduction in GFR is thus necessary for the maintenance of chronic metabolic alkalosis. Normalizing GFR induces bicarbonaturia and initiates repair of the alkalosis.

Alkalosis↗
PubMed1985

Renal mechanism of action of rat atrial natriuretic factor.

There has been conflict as to whether crude extracts of atrial natriuretic factor increase renal solute excretion by a hemodynamic mechanism or by direct inhibition of tubular transport. To investigate this issue, seven rats were studied during a euvolemic control period and following continuous administration of pure, synthetic 24 amino acid atrial natriuretic factor. A 10-25-fold increase in urinary sodium and chloride excretion occurred with a brisk kaliuresis but little bicarbonaturia. Atrial natriuretic factor caused whole kidney glomerular filtration rate to increase from 1.17 +/- 0.04 to 1.52 +/- 0.07 ml/min (P less than 0.005). A parallel increase in single nephron glomerular filtration rate, from 34 +/- 1 to 44 +/- 2 nl/min (P less than 0.001), and from 26 +/- 1 to 37 +/- 2 nl/min (P less than 0.005) was measured at the end-proximal and early distal nephron sites, respectively. Appropriate for the higher flows were an increase in absolute proximal and loop reabsorptive rates for bicarbonate, chloride, and water, with a slight decrease in fractional solute and volume reabsorption in proximal and loop segments. To exclude the possibility that atrial natriuretic factor increased filtration rate only in anesthetized animals, eight unanesthetized rats were studied. Glomerular filtration rate increased by 45%, from 2.04 +/- 0.17 to 2.97 +/- 0.27 ml/min (P less than 0.005) without significant change in renal plasma flow, as reflected by 14C-para-aminohippurate clearance (5.4 +/- 0.5-5.6 +/- 0.9 ml/min). The clearance and micropuncture data did not preclude changes in relative blood flow distribution to or in transport by deep nephron segments. In conclusion, atrial natriuretic factor appears to increase renal solute excretion predominantly by a hemodynamic mechanism without directly inhibiting superficial tubular transport.

Animals↗
PubMed1985

Active and passive components of NaCl absorption in the proximal convoluted tubule of the rat kidney.

The active and passive components of NaCl absorption were examined in doubly perfused proximal convoluted tubules (PCT) of the rat kidney. When anion concentration gradients were generated by perfusing the lumen with a high chloride, low bicarbonate solution and the peritubular capillaries with a complete solution resembling plasma ultrafiltrate, volume absorption (JV) was 1.79 nl/mm/min and estimated chloride absorption (JCl) was 270 pEq/mm/min. When anion gradients were eliminated by perfusing the peritubular capillaries with a high chloride solution, JV was reduced to 0.91 nl/mm/min and JCl to 140 pEq/mm/min. These residual rates of absorption were reduced to zero by removing potassium from the perfusates. In the presence of anion gradients, removal of potassium reduced JV from 1.79 to 0.60 nl/mm/min and JCl from 270 to 90 pEq/mm/min. It is concluded that: (1) when PCT lumen are perfused with high chloride solution and the peritubular capillaries perfused with an ultrafiltrate-like solution, approximately 50% of NaCl and water absorption is passive, driven by the anion gradients, and 50% is active; (2) when PCT lumen and peritubular capillaries are both perfused with high chloride solution, anion gradients are absent and all NaCl absorption is active.

Animals↗
PubMed1984

Reduced glomerular filtration and enhanced bicarbonate reabsorption maintain metabolic alkalosis in humans.

The mechanism that sustains chloride-depletion metabolic alkalosis is presumed to be a stimulation of renal acidification, so that the elevated filtered bicarbonate load that attends hyperbicarbonatemia is completely reabsorbed. However, such enhancement of renal bicarbonate reabsorption is not necessary to maintain hyperbicarbonatemia if the filtered bicarbonate load is not increased owing to a concomitant reduction in glomerular filtration rate (GFR). To assess the relative contributions of enhanced renal bicarbonate reabsorption and reduced GFR in the maintenance of chloride-depletion alkalosis in humans, selective hydrochloric acid depletion was induced in five normal subjects. Plasma bicarbonate concentration increased by 27% (25.3 +/- 0.1 to 32.1 +/- 0.3 mEq/liter, P less than 0.005), whereas the rate of renal bicarbonate reabsorption increased by only 17% (2.7 +/- 0.1 to 3.2 +/- 0.2 mEq/min, P less than 0.05) owing to a 10% reduction in GFR (93.2 +/- 4.4 to 84.3 +/- 4.1 ml/min, P less than 0.01). Thus, in chloride-depletion metabolic alkalosis in humans, the increase in plasma bicarbonate concentration is not attended by a commensurate increase in filtered bicarbonate and rate of renal bicarbonate reabsorption. Both a reduction in GFR and an enhancement of renal bicarbonate reabsorption contribute to maintenance of the alkalotic state.

Absorption↗
PubMed1984

Effects of acute alterations in PCO2 on proximal HCO-3, Cl-, and H2O reabsorption.

The effect of acute changes in arterial PCO2 on absolute proximal reabsorption of bicarbonate, chloride, and water has not been systematically studied. In the present free-flow micropuncture studies in Munich-Wistar rats, arterial PCO2 was increased or decreased by 20 mmHg. Under conditions of stable SNGFR, proximal and whole kidney electrolyte reabsorption was measured. Acute hypocapnia decreased absolute proximal bicarbonate reabsorption by 23% (from 1,008 +/- 38 to 773 +/- 36 pmol/min). Proximal volume reabsorption also decreased. Although bicarbonate delivery out of the superficial proximal convoluted tubule did not exceed normal levels, bicarbonaturia developed, suggesting an additional suppression of acidification by distal and/or juxtamedullary nephron segments. Acute hypercapnia increased absolute proximal bicarbonate reabsorption by only 10% in chronically alkalotic animals (from 1,050 +/- 68 to 1,176 +/- 77 pmol/min). In acutely alkalotic animals, hypercapnia caused no significant increment in the higher basal level of absolute proximal bicarbonate reabsorption (from 1,158 +/- 120 to 1,234 +/- 97 pmol/min). Whole kidney bicarbonate reabsorption rose, again suggesting a distal and/or juxtamedullary effect. Hypercapnia inhibited proximal chloride reabsorption and caused a chloruresis. In conclusion, acute hypo- and hypercapnia caused alterations in proximal bicarbonate, chloride, and sodium transport that may participate, at least in part, in the changes in whole kidney electrolyte reabsorption observed in these conditions. Distal and/or juxtamedullary nephrons also appeared to contribute to the changes in renal acidification induced by alterations in systemic PCO2.

Absorption↗
PubMed1984

Regulation of proximal bicarbonate reabsorption.

Under free-flow conditions, alterations in acid-base and extracellular volume status affect absolute proximal bicarbonate reabsorption. Microperfusion studies have characterized the individual determinants of the active and passive components of proximal acidification. These determinants include luminal bicarbonate concentration, luminal flow rate, peritubular bicarbonate concentration, PCO2, extracellular volume status, and solute-solvent interactions. When these individual determinants are integrated into a computer-simulated model of absolute proximal bicarbonate reabsorption, the results agree well with the in vivo free-flow data.

Absorption↗
PubMed1984

Axial heterogeneity in the rat proximal convoluted tubule. I. Bicarbonate, chloride, and water transport.

To measure simultaneously the concentration profiles of bicarbonate, chloride and inulin along the length of the superficial proximal convoluted tubule, free-flow micropuncture measurements were made sequentially from the end-proximal tubule to Bowman's space in 10 tubules of hydropenic Munich-Wistar rats. Bicarbonate and volume reabsorption were 354 +/- 21 pmol X mm-1 X min-1 and 5.9 +/- 0.4 nl X mm-1 X min-1 in the first millimeter and fell progressively in the remaining 3.8 mm of tubule, averaging 83 +/- 4 pmol X mm-1 X min-1 and 2.3 +/- 0.5 nl X mm-1 X min-1, respectively. The values in the initial millimeter represents a high transport capacity since they exceed rates that have been observed when comparable or even higher mean luminal substrate concentrations were presented to the late proximal tubule. In contrast, chloride reabsorption was only 206 +/- 55 peq X mm-1 X min-1 in the first millimeter compared with a mean of 306 +/- 22 peq X mm-1 X min-1 in the rest of the tubule. In conclusion, there is substantial axial transport heterogeneity, with bicarbonate and water reabsorption higher but chloride reabsorption lower in the early compared with the late superficial proximal convoluted tubule.

Animals↗
PubMed1984

Axial heterogeneity in the rat proximal convoluted tubule. II. Osmolality and osmotic water permeability.

To assess whether proximal luminal fluid becomes hypotonic with respect to plasma, free-flow micropuncture measurements were made sequentially from the end-proximal tubule to Bowman's space in 10 tubules of hydropenic Munich-Wistar rats. Osmolality in Bowman's space was 2.8 +/- 0.3 mosmol less than in plasma. Tubular fluid osmolality fell along the tubule and by the end-proximal tubule was 7.5 +/- 0.7 mosmol/kg less than in plasma or 4.7 mosmol/kg less than in Bowman's space. Since luminal fluid became hypotonic, the reabsorbate was hypertonic. The transepithelial osmotic water permeability (Pf) was calculated using simultaneously measured water reabsorption rates. The osmotic gradient responsible for water reabsorption was assumed to be either lumen-to-reabsorbate or lumen-to-peritubular plasma, with a reflection coefficient for sodium chloride of 0.7-1.0. The Pf was then estimated to be between 0.2 and 2.0 cm/s in the first millimeter of tubule and to have fallen to 0.1-0.2 cm/s by the end of the tubule. In conclusion, luminal hypotonicity develops in the rat proximal convoluted tubule and must be considered as part of the osmotic driving force for water reabsorption.

Animals↗
PubMed1984

Chronic hypercapnia stimulates proximal bicarbonate reabsorption in the rat.

The hyperbicarbonatemia of chronic respiratory acidosis might be maintained by a reduction in filtration rate or an enhancement of tubular bicarbonate reabsorption. To investigate this question, 12 Munich-Wistar rats were exposed to a 10% CO2 atmosphere for 6-8 d. Chronic respiratory acidosis developed, with arterial pH 7.30 +/- 0.01, partial pressure of CO2 (pCO2) 80 +/- 2 mmHg, and total CO2 concentration 45 +/- 1 mM. Single nephron glomerular filtration rate was normal (42 +/- 1 nl/min). Chronic hypercapnia caused absolute proximal reabsorption to be significantly stimulated (1,449 +/- 26 pmol/min) as compared with reabsorption previously observed in normal animals (1,075 +/- 74 pmol/min) or in animals subjected to acute hypercapnia (1,200 +/- 59 pmol/min). This is the first demonstration that proximal bicarbonate reabsorption can be stimulated above normal euvolemic values. When eight animals were subsequently allowed to return toward a normocapnic state (arterial pCO2 46 +/- 1 mmHg) over the course of 1-1.5 h, bicarbonate reabsorption was still significantly higher (1,211 +/- 34 pmol/min) than in similarly alkalotic, normocapnic control groups (994 +/- 45 pmol/min). In conclusion, chronic, but not acute, hypercapnia stimulates absolute proximal bicarbonate reabsorption to exceed the level found in normal euvolemic rats.

Absorption↗
PubMed1983

Volume expansion predominantly inhibits proximal reabsorption of NaCl rather than NaHCO3.

The present study quantitated the effect of extracellular volume expansion on absolute proximal bicarbonate, chloride, and water reabsorption in 10 Sprague-Dawley rats. Paired free-flow micropuncture measurements were made in the plasma-replete euvolemic state and following 10% body wt isohydric, colloid-free volume expansion. Single nephron glomerular filtration rate and glomerular ultrafiltrate concentration of bicarbonate and chloride were similar in the two conditions. Volume expansion caused absolute proximal reabsorption of bicarbonate to fall by only 7% (from 987 +/- 39 to 920 +/- 53 pmol/min, P less than 0.05). This decrement in bicarbonate reabsorption was compatible with the known increase in bicarbonate permeability and backleak induced by expansion. In contrast, a marked 26% fall in absolute proximal chloride reabsorption occurred (from 1,601 +/- 147 to 1,180 +/- 149 peq/min, P less than 0.005), attributed to alteration in transcellular rather than passive sodium chloride transport. Thus, the decrease in absolute proximal volume reabsorption (from 19.7 +/- 1.0 to 16.7 +/- 1.2 nl/min, P less than 0.005) induced by volume expansion was predominantly a consequence of inhibition of sodium chloride rather than sodium bicarbonate reabsorption.

Absorption↗
PubMed1983

Flow dependence of proximal tubular bicarbonate absorption.

Rat proximal convoluted tubules were microperfused in vivo to examine the effect of flow rate on bicarbonate absorption. When tubules were perfused with 25 mM bicarbonate, increases in perfusion rate from 15 to 33 to 49 nl/min caused bicarbonate absorption to increase from 105 +/- 4 to 176 +/- 8 to 209 +/- 7 pmol X mm-1 X min-1, respectively. Only 15% of this stimulation could be attributed to a flow-induced increase in the measured axial luminal bicarbonate concentration profile. In addition, effects of flow on passive bicarbonate diffusion or convection could not account for the observed stimulation. When tubules were perfused with 58 mM bicarbonate (a concentration previously shown to achieve maximal rates of proton secretion), increasing flow rate from 15 to 49 nl/min did not stimulate bicarbonate absorption. Thus, when examined as a function of mean luminal bicarbonate concentration, increases in flow increased the rate of proton secretion without affecting the maximal rate. The data are most consistent with flow-dependent stimulation of bicarbonate absorption, secondary to flow-dependent changes in luminal bicarbonate concentration, occurring by two mechanisms: 1) flow-dependent increases in the measured axial luminal bicarbonate concentration profile and 2) flow-dependent decreases in radial luminal bicarbonate concentration gradients.

Absorption↗
PubMed1983

Effects of extracellular fluid volume and plasma bicarbonate concentration on proximal acidification in the rat.

The effects of systemic bicarbonate concentration and extracellular fluid volume status on proximal tubular bicarbonate absorption, independent of changes in luminal composition and flow rate, were examined with in vivo luminal microperfusion of rat superficial proximal convoluted tubules. Net bicarbonate absorption and bicarbonate permeability were measured using microcalorimetry. From these data, net bicarbonate absorption was divided into two parallel components: proton secretion and passive bicarbonate diffusion. The rate of net bicarbonate absorption was similar in hydropenic and volume-expanded rats when tubules were perfused with 24 mM bicarbonate, but was inhibited in volume-expanded rats when tubules were perfused with 5 mM bicarbonate. Volume expansion caused a 50% increase in bicarbonate permeability, which totally accounted for the above inhibition. The rate of proton secretion was unaffected by volume expansion in both studies. The rate of net bicarbonate absorption was markedly inhibited in alkalotic expansion as compared with isohydric expansion. Bicarbonate permeabilities were not different in these two conditions, and the calculated rates of proton secretion were decreased by greater than 50% in alkalosis. Net bicarbonate absorption was stimulated in acidotic rats compared to hydropenic rats. This stimulation was attributable to a 25% increase in the rate of proton secretion. We conclude that (a) proton secretion is stimulated in acidosis, inhibited in alkalosis, and is not altered by volume status; (b) bicarbonate permeability is increased by volume expansion but is not altered by increases in plasma bicarbonate concentration; (c) when luminal bicarbonate concentrations are similar to those of plasma, net bicarbonate absorption is dominated by proton secretion and is thus sensitive to peritubular bicarbonate concentrations, and insensitive to extracellular fluid volume; (d) when luminal bicarbonate concentrations are low and proton secretion is slowed, bicarbonate permeability and thus extracellular fluid volume have a greater influence on net bicarbonate absorption.

Absorption↗
PubMed1983

Metabolic alkalosis in the rat. Evidence that reduced glomerular filtration rather than enhanced tubular bicarbonate reabsorption is responsible for maintaining the alkalotic state.

Maintenance of chronic metabolic alkalosis might occur by a reduction in glomerular filtration rate (GFR) without increased bicarbonate reabsorption or, alternatively, by augmentation of bicarbonate reabsorption with a normal GFR. To differentiate these possibilities, free-flow micropuncture was performed in alkalotic Munich-Wistar rats with a glomerular ultrafiltrate total CO2 concentration of 46.5 +/- 0.9 mM (vs. 27.7 +/- 0.9 mM in controls). Alkalotic animals had a markedly reduced single nephron GFR compared with controls (27.4 +/- 1.5 vs. 51.6 +/- 1.6 nl/min) and consequently unchanged filtered load of bicarbonate. Absolute proximal bicarbonate reabsorption in alkalotic animals was similar to controls (981 +/- 49 vs. 1,081 +/- 57 pmol/min), despite a higher luminal bicarbonate concentration, contracted extracellular volume, and potassium depletion. When single nephron GFR during alkalosis was increased toward normal by isohydric volume expansion or in another group by isotonic bicarbonate loading, absolute proximal bicarbonate reabsorption was not substantially augmented and bicarbonaturia developed. To confirm that a fall in GFR occurs during metabolic alkalosis, additional clearance studies were performed. Awake rats were studied before and after induction of metabolic alkalosis associated with varying amounts of potassium and chloride depletion. In all cases, the rise in blood bicarbonate concentration was inversely proportional to a reduction in GFR; filtered bicarbonate load remained normal. In conclusion, a reduction in GFR is proposed as being critical for maintaining chronic metabolic alkalosis in the rat. Constancy of the filtered bicarbonate load allows normal rates of renal bicarbonate reabsorption to maintain the alkalotic state.

Absorption↗
PubMed1983

NaHCO3 therapy corrects the increased urinary Na, K, Cl and H2O excretion induced by NH4Cl.

Micropuncture studies conflict as to whether the proximal volume reabsorptive defect of acute hyperchloremic metabolic acidosis corrects when the acidosis is repaired with NaHCO3. Whether NaHCO3 improves the elevation in urinary solute and water excretion rates induced by acidosis in euvolemic animals, reflecting normalization of proximal reabsorption, has not been previously examined. In these studies in awake rats, NH4Cl caused the plasma bicarbonate concentration to fall from 22 to 11 mEq/l concomitantly with a 1 1/2- to 3-fold increase in sodium, potassium, chloride and volume urinary excretion rates. Isotonic NaHCO3 (5% body weight) infusion restored the plasma bicarbonate concentration to 21 mEq/l and urinary electrolyte and volume excretion rates returned to control values. Comparable volume expansion with NaCl did not correct the acidosis or improve urinary excretion rates. We conclude that correction of acute metabolic acidosis by NaHCO3 therapy repairs the natriuresis, kaluresis, chloruresis and diuresis, presumably by improving proximal reabsorption.

Acidosis↗