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Biomedical subjects

C M Bennett

Publications and source records attributed to C M Bennett.

At least 37 records · Page 2Linked to original sources
PubMed1977

Episodic secretion of arginine vasopressin.

The plasma arginine vasopressin (pAVP) response to osmotic stimulation was studied in dogs and sheep by sampling at frequent intervals during steady-state dehydration and during water diuresis. Frequent sampling also was conducted after continuous infusion or bolus injection of 5 or 20 g/100 ml NaCl. A pulsatile pattern of pAVP was observed after such infusions or injections and in some animals after water deprivation. This pattern was not seen after water loading or in mildly dehydrated animals. The short term changes in pAVP during continuous infusion of 5 g/100 ml NaCl could not be correlated with variations in plasma tonicity. Rather, they appeared to reflect discontinuous hypothalamic posterior pituitary release of AVP. Thirst was evoked by a lower dose of 5 g/100 ml NaCl than was required for consistent stimulation of pAVP release, and the thirst response frequently was observed prior to the peak AVP response after bolus injection of 5 and 20 g/100 ml NaCl.

Animals↗
PubMed1977

Structure of a juxtaglomerular cell tumor: the presence of a neural component: a light and electron microscopic study.

A 15-year-old girl with hypertension, markedly elevated plasma renin activity, and normal aortogram had a well encapsulated tumor nodule removed from the right kidney. Following surgery, the plasma renin activity and blood pressure became normal and have remained so for the past 12 months. The tumor consisted of juxtaglomerular cells filling the interstitium between endothelium-lined vascular spaces. Electron microscopy disclosed the presence in the interior of the tumor, of unmyelinated nerve bundles with varicosities containing the small, densely cored vesicles characteristic of adrenergic nerves. Nerve terminals were in contact with the juxtaglomerular tumor cells. No basement membrane material was interposed between the nerve endings and the tumor cell; the width of the gap between the two plasma membranes was approximately 150 A. The presence of sympathetic fibers in the juxtaglomerular cell tumor underscores the close biologic relationship between the sympathetic and renin systems.

Adolescent↗
PubMed1976

Double-blind comparison of minoxidil and hydrallazine in severe hypertension.

1. Thirty moderately severely hypertensive patients were studied in a double-blind comparison of minoxidil and hydrallazine in combination with frusemide and propranolol. 2. Blood pressure control in both groups of patients was satisfactory but long-term control appeared to be better in the minoxidil group. 3. Renal function was well preserved in both groups. Evidence of cardiac hypertrophy was slow to resolve despite good control of blood pressure. Side effects were negligible, and patient acceptance and rehabilitation was excellent.

Adult↗
PubMed1976

Permselectivity of of the glomerular capillary wall. Studies of experimental glomerulonephritis in the rat using neutral dextran.

Polydisperse [3h] dextran was infused into eight Munich-Wistar rats in the early autologous phase of nephrotoxic serum nephritis (NSN), thereby permitting direct measurements of pressures and flows in surface glomeruli and fractional clearances for dextrans [(U/P) dextran/(U/P) inulin] ranging in radius from 18 to 42 A. Despite glomerular injury, evidenced morphologically and by a marked reduction in the glomerular capillary ultrafiltration coefficient, the glomerular filtration rate remained normal because of a compensating increase in the mean net ultrafiltration pressure. In NSN rats, as in normal controls, inulin was found to permeate the glomerular capillary wall without measurable restriction, and dextrans were shown to be neither secreted nor reabsorbed. For dextran radii of 18, 22, 26, 30, 34, 38, and 42 A, (U/P) dextran/(U/P) inulin in NSN and control rats, respectively, averaged 0.90 vs. 0.99, 0.81 vs. 0.97, 0.63 vs. 0.83, 0.38 vs 0.55, 0.20 vs. 0.30, 0.08 vs. 0.11, and 0.02 vs. 0.03. Using a theory based on macromolecular transport through pores, the results indicate that in NSN rats, effective pore radius is the same as in controls, approximately 50 A. In NSN, however, the ratio of total pore surface area to pore length, a measure of the number of pores, is reduced to approximately 1/3 that of control, probably due to a reduction in capillary surface area. These results suggest that proteinuria in glomerular disease is not due simply to increases in effective pore radius or number of pores, as previously believed. Using a second theoretical approach, based on the Kedem-Katchalsky flux equations, dextran permeability across glomerular capillaries was found to be slightly lower, and reflection coefficient slightly higher in NSN than in control rats.

Animals↗
PubMed1976

Permselectivity of the glomerular capillary wall. Studies of experimental glomerulonephritis in the rat using dextran sulfate.

To determine whether the increased filtration of serum proteins after glomerular injury is the consequence of altered electrostatic properties of the glomerular capillary wall, we measured fractional clearances of the anionic polymer, dextran sulfate, in nine Munich-Wistar rats in the early autologous phase of nephrotoxic serum nephritis (NSN). In agreement with previous studied from this laboratory, whole kidney and single nephron glomerular filtration rates were normal in NSN rats despite histological evidence of glomerular injury, and despite a marked reduction in the glomerular capillary ultrafiltration coefficient to approximately one-third of normal. In the companion study (9), it was shown that in NSN rats the mean fractional clearances of neutral dextrans over the range of effective molecular radii from 18 to 42 A were reduced, compared to normla. In contrast, in the present study the mean fractional clearances for dextran sulfate over the same range of molecular radii were significantly greater than those found previously for normal Munich-Wistar rats. The fractional clearance of dextran sulfate molecules of the same molecular radius as serum albumin (approximately 36 A) was increased markedly, from 0.015 +/- 0.005 (SEM) in nonnephritic controls to 0.24 +/- 0.03 in NSN (P less than 0.001). The sialoprotein content of glomeruli, estimated by the colloidal iron reaction, was reduced in NSN rats as compared to normal controls. It is concluded that the abnormal filtration of anionic serum proteins, such as albumin, seen in glomerulopathies is, at least in part, the consequence of loss of fixed negative charges from the glomerular capillary wall.

Animals↗
PubMed1976

The renal sympathetic system and juxtaglomerular cells in experimental renovascular hypertension.

Marked reduction of the monoaminergic nerve fluorescence and catecholamine tissue content were demonstrated in the ischemic kidney of rats made hypertensive by unilateral renal artery stenosis (two-kidney Goldblatt hypertension). The nonischemic kidney showed a normal degree of fluorescence and catecholamine content. The electron microscope failed to demonstrate recognizable nerves around most of the glomerular arterioles of the ischemic kidney, whereas a normal rich innervation was observed in the nonischemic side. The juxtaglomerular index and renal renin content were elevated in the ischemic kidney and markedly reduced in the nonischemic kidney. Juxtaglomerular cells were present in the glomerular mesangium and ultrastructurally showed changes consistent with increased renin synthesis. The extent of disruption of the sympathetic system in renal hypertension might play a role in the degree of hypersecretory response of the juxtaglomerular cells to renal artery constriction.

Animals↗
PubMed1975

Traumatic renal artery thrombosis with acute malignant hypertension and hyperreninemia.

Renal arterial thrombosis from blunt trauma causes delayed hypertension in many patients, but few reports have been well documented. This first report of immediate onset of malignant hypertension in a patient following blunt renal trauma, with documented histologic and renal vein renin data, stresses the pitfalls associated with the diagnosis and treatment of this condition.

Humans↗
PubMed1975

Glomerular-tubular balance for bicarbonate in the dog.

Previous work that apparently showed a functional relationship between GFR and maximum bicarbonate reabsorption was done at a time when the effects on the latter of several factors (PCO2, plasma potassium concentration, and extracellular fluid volume expansion) were not recognized. The present study re-examines this relationship, while controlling these factors. In 14 hydropenic dogs, bicarbonate reabsorption per unt GFR increased linearly with increases in plasma bicarbonate concentration. At any level of plasma bicarbonate concentration,the absolute rate of bicarbonate reabsorption was functionally related to the GFR. In six volume-expanded dogs, bicarbonate reabsorption remained stable at 20-22 mmol/liter GFR as plasma bicarbonate was raised to greater than 40mM. The absolute rate of bicarbonate reabsorption increased with large increases in GFR induced by methylprednisolone and high-protein diet. In a third group of dogs, bicarbonate reabsorption varied directly with increases in GFR, while plasma bicarbonate concentration was held relatively constant above the threshold. We conclude there is a close functional relationship between the absolute rate of bicarbonate reabsorption and GFR in individual dogs.

Animals↗
PubMed1975

Glomerular-tubular balance for bicarbonate in man.

We recently showed in dogs that there is a close relationship between bicarbonate reabsorption and glomerular filtration rate (GFR). The present studies were designed to confirm these findings in five normal men. Bicarbonate titrations were done after ingesting a low protein diet for one week and were repeated following elevation of GFR 11-29 per cent by high protein diet and dexamethazone ingestion. In every casetubular reabsorption of bicarbonate increased in proportion to the increases in GFR. We conclude that glomerular-tubular balance for bicarbonate reabsorption is a characteristic of human, as well as canine kidneys.

Absorption↗
PubMed1975

Determinants of glomerular filtration in experimental glomerulonephritis in the rat.

Pressures and flows were measured in surface glomerular capillaries, efferent arterioles, and proximal tubules of 22 Wistar rats in the early autologous phase of nephrotoxic serum nephritis (NSN). Linear deposits of rabbit and rat IgG and C3 component of complement were demonstrated in glomerular capillary walls by immunofluorescence microscopy. Light microscopy revealed diffuse proliferative glomerulonephritis, and proteinuria was present. Although whole kidney and single nephron glomerular filtration rate (GFR) in NSN (0.8 plus or minus 0.04 SE2 ml/min and 2 plus or minus 2 nl/min, respectively) remained unchanged from values in 16 weight-matched NORMAL HYDROPENIC control rats (0.8 plus or minus 0.08 and 28 plus or minus 2), important alterations in glomerular dynamics were noted. Mean transcapillary hydraulic pressure difference (deltaP) averaged 41 plus or minus 1 mm Hg in NSN versus 32 plus or minus 1 in controls (P LESS THAN 0.005). Oncotic pressures at the afferent (piA) end of the glomerular capillary were similar in both groups ( 16 mm /g) but increased much less by the efferent end (piE) in NSN (to 29 plus or minus 1 mm Hg) than in controls (33 plus or minus 1, P less than 0.025). Hence, equality between deltaP and piE, denoting filtration pressure equilibrium, obtained in control but not in NSN rats. While glomerular plasma flow rate was slightly higher in NSN (88 plus or minus 8 nl/min) than in controls (76 plus or minus 6, P greater than 0.2), the failure to achieve filtration equilibrium in NSN rats was primarily the consequence of a marked fall in the glomerular capillary ultrafiltration coefficient, Kf, to a mean value of 0.03 nl/(s times mm Hg), considerably lower than that found recently for the normal rat, 0.08 nl/(s times mm Hg). Thus, despite extensive glomerular injury, evidenced morphologically and by the low Kf, GFR remained normal. This maintenance of GFR resulted primarily from increases in deltaP, which tended to increase the net driving force for filtration, and thereby compensate for the reduction in Kf.

Animals↗
PubMed1975

Control of proximal tubule fluid reabsorption in experimental glomerulonephritis.

We have recently shown that in the early autologous phase of nephrotoxic serum nephritis (NSN) single nephron glomerular filtration rate is unchanged from values in normal hydropenic control rats, but that single nephron filtration fraction and efferent arteriolar oncotic pressure (piE) are reduced because of a marked reduction in the glomerular capillary ultrafiltration coefficient. The present study was undertaken to examine the influence of this decline in piE as well as the other known determinants of peritubular capillary fluid exchange on absolute proximal fluid reabsorption (APR) in NSN. The findings indicate that APR and proximal fractional reabsorption are reduced significantly in NSN, relative to values in a separate group of age and weight-matched normal hydropenic control rats studied concurrently. In addition to the measured decline in piE, efferent arteriolar plasma flow (Qe) and peritubular capillary hydraulic pressure (Pc) were found to increase significantly, while interstitial oncotic pressure, estimated from hilar lymph, was not significantly different from values in control rats. Using a mathematical model of peritubular capillary fluid uptake we found that, assuming that the capillary permeability-surface area product and interstitial hydraulic pressure are unchanged in NSN, the observed changes in piE and Pc are sufficient to offset the effect of the increase in QE, yielding a calculated reduction in APR of approximately 4 nl/min, in excellent agreement with the observed mean decline of 4.1 nl/min. These findings suggest that control of APR in NSN is mediated by the same factors that regulate APR under normal physiological conditions, namely, the imbalance of forces governing peritubular capillary uptake of isotonic reabsorbate.

Animals↗
PubMed1973

Effect of extracellular volume expansion upon sodium reabsorption in the distal nephron of dogs.

Micropuncture studies have disclosed that extracellular fluid (ECF) volume expansion inhibits sodium reabsorption in the proximal tubule. The diuresis that ensues represents only a portion of the increment in sodium and water escaping proximal reabsorption, since a large and variable fraction of the increment is reabsorbed distally. In certain experimental models proximal reabsorption may be depressed by ECF volume expansion, yet only a negligible amount of sodium appears in the final urine. This suggests that saline diuresis is the consequence of depressed distal sodium reabsorption. Previous clearance and micropuncture studies have not conclusively proven this. Eight dogs were studied repeatedly: in some studies glomerular filtration rate and distal delivery were increased markedly without sodium administration; in others comparably high distal sodium loads were achieved by progressive 1/2 isotonic saline infusion. C(H2O) at high distal sodium loads was depressed by expansion of the ECF volume with hypotonic saline. The difference in free water formation between dogs which did and did not receive hypotonic saline was accounted for by the difference in sodium excretion. In one dog hypotonic saline expansion failed to depress free water formation; likewise the level of natriuresis in this dog was severely attenuated. The results of these experiments provide strong evidence that the natriuresis that occurs following ECF volume expansion with saline is a consequence of alteration in function of the distal nephron.

Albumins↗
PubMed1970

Urine concentration and dilution in hypokalemic and hypercalcemic dogs.

The urine-concentrating mechanism was studied in chronic hypokalemia (seven dogs given a low K(+), high NaCl diet plus injections of deoxycorticosterone acetate [DOCA]) and chronic hypercalcemia (seven dogs given vitamin D). In the potassium-depleted dogs, muscle, serum, and urine K(+) fell markedly, but glomerular filtration rate (GFR) and body weight varied little. Maximum urine osmolality fell in all dogs (mean decrease = 45%); however, solute-free water reabsorption (T(CH2O)) at high rates of solute excretion remained normal in three of four dogs. Free water excretion (C(H2O)) increased normally or supranormally as a function of increasing Na(+) delivery to Henle's loop in six dogs so tested. Hypercalcemia of several weeks duration caused a decrease in both GFR (mean 36%) as well as in maximum urine osmolality (mean 57%). Maximum T(CH2O) was not invariably depressed; in fact, when the values were adjusted for the reduced number of functioning nephrons (T(CH2O)/C(In)), four of seven studies were normal. C(H20)/C(In) increased normally (or supranormally) with increasing fractional Na delivery to Henle's loop in four of five dogs.I conclude that the lowered maximum urine osmolality in these hypokalemic and hypercalcemic dogs was not related to abnormal water reabsorption from the collecting ducts. Although not specifically measured in this study, it is very likely that solute accumulation in the renal medulla was reduced. This probably was not caused by abnormal delivery of sodium to, nor reabsorption of sodium from Henle's loop. It is likely that a more subtle defect exists in the countercurrent mechanisms for establishing a steep concentration gradient in the renal medulla. In the few hypercalcemic dogs in whom GFR was very low, I believe that injury to, and blockage of medullary tubules could account for most of the reduction in maximum U(Osm). Although not specifically ruled out, there is no evidence here to suggest that high serum Ca(+) or low serum K(+) per se causes a defect in sodium and water reabsorption in the mammalian nephron.

Animals↗
PubMed1969

Failure to demonstrate a hormonal inhibitor of proximal sodium reabsorption.

Recently, it has been reported that a humoral inhibitor of proximal sodium reabsorption could be detected in plasma, and dialysates of plasma, of rats and dogs undergoing saline diuresis. We have repeated these studies using similar techniques and protocols. Fractional sodium reabsorption by the proximal tubule (as estimated in free-flow micropuncture studies from tubule fluid-to-plasma inulin ratios) was found not to be lower during infusion of "natriuretic" plasma than during subsequent infusion of "hydropenic" plasma. Similarly, infusion of natriuretic plasma failed to prolong reabsorptive half-time of the shrinking drop beyond that seen during hydropenic plasma infusion. No increase in urine volume or rate of sodium excretion was observed during the period of natriuretic plasma infusion, nor did natriuretic plasma result in an increase in these measures in rats undergoing water diuresis. It also has been reported that dialysates of natriuretic plasma, but not of hydropenic plasma, when placed directly into the tubule lumen, inhibit proximal sodium reabsorption. In double blind studies carried out independently in Bethesda, London, and Cologne, we failed to detect the presence of a dialyzable inhibitor in natriuretic plasma. Finally, in contrast to other recent reports, we were unable to detect inhibitory activity in plasma obtained from dogs during the "escape" phase of chronic deoxycorticosterone acetate administration.

Animals↗
PubMed1968

Micropuncture study of nephron function in the rhesus monkey.

The function of the proximal and distal tubule was studied in the rhesus monkey during antidiuresis and during the diuresis after furosemide administration (during which extracellular fluid volume was maintained).In the proximal tubule, fluid to plasma ratios for sodium, potassium, and osmolality approximated unity. During antidiuresis, about 30% of the filtered water remained at the end of the accessible portion of this segment (92% of length). Fluid was hypotonic to plasma throughout the distal tubule. 25% of the filtered water was present in the early distal tubule. Small but significant water reabsorption (about 8% of filtered) occurred in remainder of this segment. Tubule fluid to plasma potassium concentration ratios tended to increase along the distal tubule, and the amount of potassium, relative to the amount filtered, increased from 13% in the early portion of this segment to 26% in the late portion.After furosemide was administered animals excreted about one-third of the filtered sodium and water. Despite this diuresis, electrolyte and water reabsorption along the proximal tubule did not differ from values obtained in control animals. Osmolality and sodium concentration of fluid from the distal tubule approached those of plasma. 22% of the filtered sodium (twice the control values) reached the distal tubule, whereas the fraction of filtered water remaining was only slightly increased. These findings indicate that, after the administration of this drug, inhibition of sodium reabsorption occurred in the water-impermeable segment of the nephron, rather than in the proximal tubule. After furosemide administration, all tubule fluid to plasma potassium concentration ratios in the distal tubule were equal to or greater than one, suggesting inhibition of active potassium reabsorption at or prior to this site.Fluid to plasma bicarbonate concentration ratios from the midportion of the proximal tubule were consistently less than one in normal monkeys. After acetazolamide was administered, the bicarbonate concentration of samples of tubule fluid recollected from these same sites was the same as, or higher than in plasma. This fact demonstrates the inhibition of bicarbonate reabsorption in this portion of the tubule.

Journal Article↗