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Biomedical subjects

C Westenfelder

Publications and source records attributed to C Westenfelder.

18 recordsLinked to original sources
PubMed1992

Evidence for cytokine-inducible nitric oxide synthesis from L-arginine in patients receiving interleukin-2 therapy.

An interferon-gamma, tumor necrosis factor, and interleukin-1-inducible, high-output pathway synthesizing nitric oxide (NO) from L-arginine was recently identified in rodents. High-dose interleukin-2 (IL-2) therapy is known to induce the same cytokines in patients with advanced cancer. Therefore, we examined renal cell carcinoma (RCC; n = 5) and malignant melanoma (MM; n = 7) patients for evidence of cytokine-inducible NO synthesis. Activity of this pathway was evaluated by measuring serum and urine nitrate (the stable degradation product of NO) during IL-2 therapy. IL-2 administration caused a striking increase in NO generation as reflected by serum nitrate levels (10- and 8-fold increase [P less than 0.001, P less than 0.003] for RCC and MM patients, respectively) and 24-h urinary nitrate excretion (6.5- and 9-fold increase [both P less than 0.001] for RCC and MM patients, respectively). IL-2-induced renal dysfunction made only a minor contribution to increased serum nitrate levels. Metabolic tracer studies using L-[guanidino-15N2]arginine demonstrated that the increased nitrate production was derived from a terminal guanidino nitrogen atom of L-arginine. Our results showing increased endogenous nitrate synthesis in patients receiving IL-2 demonstrate for the first time that a cytokine-inducible, high-output L-arginine/NO pathway exists in humans.

Adult↗
PubMed1990

Volume homeostasis in calves with artificial atria and ventricles.

We examined whether replacement of cardiac atria and ventricles with total artificial hearts (TAH), a procedure that removes cardiac nerves and all sources of atrial natriuretic factor (ANF), would cause alterations in volume homeostasis in awake calves. Preoperatively, extracted plasma immunoreactive (ir)ANF levels were 13.3 +/- 0.6 and remained postoperatively at 10.5 +/- 0.4 pg/ml (P less than 0.01). TAH implantation caused systemic and pulmonary hypertension (P less than 0.01), salt retention, edema, and significant elevations of plasma renin, aldosterone, and arginine vasopressin. In intact calves rapid infusion of 6 liters of normal saline raised irANF levels to 73.7 +/- 6.5 pg/ml (P less than 0.01) and elicited a large natriuresis and diuresis. No such response to 6 liters of normal saline was obtained after calves had recovered from TAH implantation. Reduction of cardiac output (CO) by 50% caused further salt retention and no change in irANF levels. Elevation of CO back to and 33% above base line produced only a diuresis, whereas salt retention persisted and irANF levels remained unchanged. The same maneuvers elicited in surgical control calves (artificial ventricles only, largely intact atria) a significant increase in irANF levels and a diuresis and natriuresis. In conclusion, alterations in volume homeostasis observed after TAH implantation seem to be the consequence of at least two pathophysiological mechanisms: 1) functional ANF "deficiency," characterized by apparently unregulated ANF secretion from noncardiac sites, and 2) cardiac denervation.

Animals↗
PubMed1989

Secretion of atrial natriuretic peptide (ANP) from fish atrial and ventricular myocytes in tissue culture.

Primary cultures of atrial and ventricular myocytes (approx. 1 x 10(5) cells/culture) were prepared from adult teleost fish Gila atraria and maintained for 10 days. Immunoreactive atrial natriuretic peptide (ir-ANP) from fish atrial and ventricular cells was 3.9 and 2.8 ng/culture respectively, values not significantly different. Atriocytes from rat and mouse secreted comparable amounts of ANP which were not significantly different from atrial fish cultures (5.2 and 4.3 ng/culture). In contrast, their ventricular myocytes secreted only small quantities of ANP (0.8 and 0.3 ng/culture). When analyzed by reversed-phase HPLC, the media of both fish atrial and ventricular myocytes contained a peptide which exhibited properties similar to authentic human ANP (Ser 99-Tyr 126), suggesting a significant degree of sequence homology between fish and mammalian ANP. Fish ventricular cells, unlike normal mammalian ventricular cells, secrete substantial quantities of immunoreactive-ANP.

Animals↗
PubMed1988

In vivo renal angiotensin converting enzyme activity decreases in glycerol-induced acute renal failure.

We previously demonstrated that intrarenal angiotensin II generation during glycerol-induced acute renal failure was attenuated, which may have resulted from the inability of intrarenal converting enzyme to convert renal angiotensin I to angiotensin II. In order to test this hypothesis in vivo, we determined the ability of the kidney to convert angiotensin I to angiotensin II by measuring the decrease in renal cortical blood flow (RCBF) in response to exogenous angiotensin I administration. Changes in RCBF were monitored by laser-Doppler velocimetry. Three groups of rats were studied: Group I, controls (N = 7); 24 hours prior to study Group II animals were injected with 50% glycerol, 8 ml/kg i.m. (N = 4); and Group III rats were injected with mercuric chloride, 3 mg/kg s.c. (N = 5). All experimental animals had a three- to sixfold rise in serum creatinine. Mean glomerular filtration rate (GFR) of the left and right kidney in control rats was 0.7 and 0.7 ml/min, respectively. Twenty-four hours after glycerol, GFR was 0.2 ml/min in the left kidney and 0.2 ml/min in the right kidney. In HgCl2 treated rats GFR was 0.1 ml/min in the left kidney and 0.1 ml/min in the right kidney. Each of the following maneuvers elicited a similar rise in blood pressure in Groups I through III. Specifically, when first angiotensin I (4 micrograms/kg/min) was infused for three minutes; second, when 10 minutes later angiotensin I (5 micrograms) was directly applied on the left kidney; and third, when angiotensin II (5 micrograms) was topically administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1988

Atrial natriuretic factor and salt adaptation in the teleost fish Gila atraria.

It is unknown whether atrial natriuretic factor (ANF) is a mediator of environmental salt tolerance in euryhaline teleost fish. This was investigated in anesthetized Gila atraria, a euryhaline teleost native to springs of pleistocene Lake Bonneville. Plasma levels of immunoreactive (ir) ANF [using anti-human ANF-(99-126) antibodies] in fish obtained from a "fresh water" spring were significantly lower (146 +/- 27) than those in fish obtained from a "1% NaCl" spring (347 +/- 21 pg/ml, P less than 0.01). Electron micrographs of fish atrial and ventricular cardiocytes demonstrated many perinuclear granules, which closely resembled ANF-containing secretory granules seen in mammalian atriocytes. Fish heart extract contained ANF-like material of 3 kDa, which caused a marked diuresis and natriuresis in rats. In a second study, fish from a 1% NaCl spring were kept in tanks. One-third of the fish were maintained in 1% NaCl and one-third each were either adapted to fresh- or high-salt water. After 12 days, plasma irANF levels in 1% NaCl fish were 343 +/- 55, in fresh water fish 213 +/- 20 and in high-NaCl fish 691 +/- 79 pg/ml. These values differed significantly from each other (P less than 0.01). There was a close correlation between plasma irANF levels and both environmental and internal salt concentration. These data suggest that piscine ANF is an as yet unrecognized mediator of salt tolerance in this teleost and that ANF in these animals closely resembles mammalian ANF.

Acclimatization↗
PubMed1987

Failure of angiotensin converting enzyme inhibition to affect the course of chronic puromycin aminonucleoside nephropathy.

The effects of the angiotensin converting enzyme (ACE) inhibitor enalapril on the proteinuria and degree of focal glomerular sclerosis hyalinosis (FSH) in chronic puromycin aminonucleoside nephropathy (PAN) were examined. Chronic PAN was induced in male Sprague-Dawley rats by seven subcutaneous injections of puromycin aminonucleoside (20 mg/kg) over 10 weeks (Groups I and II). Group II rats also received enalapril 10 mg/kg/day in the drinking water throughout the study (12 weeks). Group III rats served as age-matched controls. Proteinuria was similar in Groups I and II (35.5 +/- 9.7 versus 29.1 +/- 4.1 mg protein/mg creatinine, mean +/- SEM, P greater than 0.05). Serum creatinine remained unchanged in Group I, but rose from 0.7 +/- 0.04 to 1.2 +/- 0.1 mg/dl (mean +/- SEM, P less than 0.05) in Group II. FSH was 13.8% in Group I, 12.9% in Group II (P greater than 0.05), and 0.6% in Group III. There was no significant difference in glomerular lipid content and in immunofluorescence for rat albumin, fibrinogen, IgM, IgG, and C3 between Groups I and II. ACE activity was inhibited by 94% in serum, 83% in lungs, and 92% in kidneys; and blood pressure response to. Angiotensin I challenge was decreased by 50% in rats similarly treated with enalapril versus controls. In summary, proteinuria and glomerular sclerosis in this model are not affected by ACE inhibition.

Angiotensin I↗
PubMed1977

Metolazone and spironolactone in cirrhosis and the nephrotic syndrome.

Eighteen patients with hepatic cirrhosis or nephrotic syndrome and having edema and/or ascites were treated during successive periods with metolazone 5 to 40 mg/day, spironolactone 100 mg/day, and with both diuretics concurrently. Metolazone alone produced a marked diuresis, natriuresis, and weight loss in 8 patients. Spironolactone alone had little effect, but the addition of metolazone renewed diuresis and natriuresis and resulted in additional substantial weight losses in all patients responsive to metolazone alone. Concurrent spironolactone and metolazone also induced moderate diuretic effects in some patients who failed to respond to either drug alone. The drugs were well tolerated; the administration of spironolactone with metolazone prevented decreases in serum potassium, which had occurred during treatment with metolazone alone.

Adult↗
PubMed1977

Effect of parathyroid hormone on urinary acidification.

The effect of parathyroid hormone (PTH) administration on urinary acidification was studied in intact and thyroparathyroidectomized dogs. PTH administration resulted in a significant increase in urine pH and HCO3 excretion. In dogs with maximally acid urine caused by Na2SO4 infusion PTH administration also led to a significant increase in urine pH and to a decrease in ammonium excretion. To examine the effect of PTH on H+ secretion in the distal nephron we measured the urine-blood (U-B) PCO2 gradient in dogs with maximally alkaline urine (urine pH greater than 7.8) before and after PTH administration. After infusion of the hormone, HCO3 excretion increased significantly but the U-B PCO2 gradient remained unchanged. The effects of PTH infusion on urinary acidification in animals with distal renal tubular acidosis caused by LiCl administration were also studied. PTH administration to these dogs increased HCO3 excretion to the same level seen in normal dogs. These data suggest that PTH does not inhibit distal H+ secretion but increases HCO3 excretion by depressing proximal HCO3 reabsorption.

Acid-Base Equilibrium↗
PubMed1977

Relationship between mineralocorticoids and renal Na+-K+-ATPase: sodium reabsorption.

To evaluate the mechanism responsible for the effect of deoxycorticosterone acetate (DOCA) on renal Na+-K+-ATPase, we compared the relative contribution of this hormone and of increased absolute sodium reabsorption (TNa) to the restoration of the enzyme in kidneys of adrenalectomized rats. In study A, adrenalectomized animals maintained on a salt-free diet received 5 mg/kg per day DOCA i.m., while sham-operated and untreated adrenalectomized rats receiving the same diet served as controls. Absolute TNa and Na+-K+-ATPase specific activity in the cortex and outer medulla of DOCA-treated rats were similar to those measured in untreated adrenalectomized animals, but were significantly lower than in sham-operated controls. In study B, the adrenalectomized rats did not receive DOCA but were fed a high salt diet and received isotonic saline, 50 ml/kg per day s.c. Absolute TNa and cortical and medullary Na+-K+-ATPase specific activity were significantly higher in the salt-loaded group than in both adrenalectomized and sham-operated rats deprived of salt. These results suggest that absolute sodium reabsorption is a major determinant of renal Na+-K+-ATPase activity, and that the effect of DOCA on this enzyme is secondary to its stimulation of absolute tubular sodium transport.

Adenosine Triphosphatases↗
PubMed1977

The critical importance of urinary concentrating ability in the generation of urinary carbon dioxide tension.

Measurement of urine to blood (U-B) carbon dioxide tension (P(CO2)) gradient during alkalinization of the urine has been suggested to assess distal H(+) secretion. A fact that has not been considered in previous studies dealing with urinary P(CO2) is that dissolution of HCO(3) in water results in elevation of P(CO2) which is directly proportional to the HCO(3) concentration. To investigate the interrelationship of urinary HCO(3) and urinary acidification, we measured U-B P(CO2) in (a) the presence of enhanced H(+) secretion and decreased concentrating ability i.e., chronic renal failure (CRF), (b) animals with normal H(+) secretion and decreased concentrating ability, Brattleboro (BB) rats, and (c) the presence of both impaired H(+) secretion and concentrating ability (LiCl treatment and after release of unilateral ureteral obstruction). At moderately elevated plasma HCO(3) levels (30-40 meq/liter), normal rats achieved a highly alkaline urine (urine pH > 7.8) and raised urine HCO(3) concentration and U-B P(CO2). At similar plasma HCO(3) levels, BB rats had a much higher fractional water excretion and failed to raise urine pH, urine HCO(3) concentration, and U-B P(CO2) normally. At a very high plasma HCO(3) (>50 meq/liter), BB rats raised urine pH, urine HCO(3) concentration, and U-B P(CO2) to the same levels seen in normals. CRF rats failed to raise urine pH, urine HCO(3), and U-B P(CO2) normally at moderately elevated plasma HCO(3) levels; at very high plasma HCO(3) levels, CRF rats achieved a highly alkaline urine but failed to raise U-B P(CO2). Dogs and patients with CRF were also unable to raise urine pH, urine HCO(3) concentration, and U-B P(CO2) normally at moderately elevated plasma HCO(3) levels. In rats, dogs, and man, U-B P(CO2) was directly related to urine HCO(3) concentration and inversely related to fractional water excretion. At moderately elevated plasma HCO(3) levels, animals with a distal acidification defect failed to raise U-B P(CO2); increasing the plasma HCO(3) to very high levels resulted in a significant increase in urine HCO(3) concentration and U-B P(CO2). The observed urinary P(CO2) was very close to the P(CO2) which would be expected by simple dissolution of a comparable amount of HCO(3) in water. These data demonstrate that, in highly alkaline urine, urinary P(CO2) is largely determined by concentration of urinary HCO(3) and cannot be used as solely indicating distal H(+) secretion.

Acid-Base Equilibrium↗
PubMed1977

Correlation of creatinine levels in saliva and plasma in normal subjects and renal patients.

Whole saliva and serum creatinine levels were evaluated in three normal subjects and 12 patients with chronic renal failure receiving regular hemodialysis treatments. Ratios of the serum vs. saliva creatinine levels ranging from 4.5 to 30.0 were found. Repeated studies also revealed marked intra-subject variations in these ratios. We conclude that the monitoring of whole saliva creatinine levels is only of limited value in accurately predicting serum or plasma creatinine levels, despite its appeal of simplicity, convenience and non-invasiveness. Its value in the qualitative monitoring of renal function may, however, be useful.

Adolescent↗
PubMed1976

Distribution of renal blood flow in dogs with congestive heart failure.

Studies were performed to determine whether the intrarenal distribution of cortical blood flow is altered in congestive heart failure. Utilizing the radioactive microsphere method, we studied eight dogs that developed congestive heart failure secondary to the construction of an aortocaval fistula. They had marked reduction in total renal blood flow not accompanied by intracortical redistribution of blood flow. All dogs had developed edema and/or ascites, and gained a mean of 3.4 kg; glomerular filtration rate, hematocrit, and urinary sodium excretion fell significantly. Renal vascular resistance increased; mean blood pressure and filtration fraction were unchanged. Furosemide was administered to a second group of nine fistula dogs. The drug produced a marked natriuresis associated with a decrease in outer cortical blood flow (zone 1) and an increase in midcortical zones 2 and 3; no change was observed in zone 4. We conclude: 1) chronic salt retention occurs in high-output heart failure in the absence of redistribution of renal cortical blood flow, and 2) the effect of furosemide on intrarenal hemodynamics of dogs with heart failure is similar to that seen in normal animals.

Animals↗
PubMed1976

Glucose and bicarbonate reabsorption in edematous dogs.

Glucose and bicarbonate reabsorption were studied in dogs made edematour by aortocaval fistula (A-V dogs) and in sham-operated dogs. Following construction of the A-V fistula, there was a significant increase in body weight; glomerular filtration rate, renal plasma flow, hematocrit, and sodium excretion decreased significantly. Bicarbonate reabosorption was significantly higher in A-V than in sham dogs both during control and volume expansion. Volume expansion depressed bicarbonate reabsorption significantly in both groups. Glucose reabsorption fell following volume expansion in both groups; glucose reabsorption was significantly higher in A-V dogs than in sham dogs during control and volume expansion. Volume expansion led to a minimal increase in sodium excretion in A-V dogs when compared to the increase in the sham dogs. These data demonsttate that chronic sodium retention is associated with enhanced reabsorption of glucose and bicarbonate. The site in the neophron responsible for the increase in reabsorption of these substances cannot be determined with certainty based on these clearance studies although it is possible that proximal reabsorption may be enhanced in this model.

Acid-Base Equilibrium↗