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Biomedical subjects

H J Kramer

Publications and source records attributed to H J Kramer.

At least 145 records · Page 8Linked to original sources
PubMed1982

Digoxin-like natriuretic activity in the urine of salt loaded healthy subjects.

In previous studies we have demonstrated a natriuretic factor of small molecular weight (less than 1,000 Daltons) in the serum and urine of salt loaded subjects. This factor isolated from salt loaded animals inhibits the Na-K-ATPase enzyme system. In addition, the natriuretic material isolated from plasma of salt-loaded dogs was shown to bind to specific digoxin antibodies. It was therefore suggested that a digitalis-like endogenous natriuretic factor (endoxin) is released in response to saline loading. In the present study we therefore investigated the presence of such an endogenous natriuretic digitalis-like activity in the urine of healthy volunteers during high salt intake. Using Sephadex G-25 for chromatographic separation of urine a material elutes as a single peak in the natriuretic post-salt fraction IV which is specifically bound to digoxin antiserum complex. Mean peak activity amounted to 1.55 +/- 0.48 ng/ml digoxin equivalents. We further purified the natriuretic material by immunoprecipitation with the digoxin antiserum complex. This purification procedure resulted in a more than 10-fold increase in specific natriuretic activity from 2.7 +/- 0.4 to 30.4 +/- 5.8 muEq Na+ x min-1 x mg-1. Thus the digitalis-like natriuretic activity previously observed in the plasma of saline loaded dogs is also present in the urine of healthy subjects during high dietary salt intake. Immunoprecipitation may offer a meaningful tool for further isolation and identification of the natriuretic hormone(s).

Adult↗
PubMed1982

Arachidonic acid metabolism in isolated rat aorta. Dependence of prostacyclin biosynthesis on extracellular potassium concentration.

Slices of rat aorta were incubated in Krebs-Ringer bicarbonate buffer for measurements of immunoreactive 6-ketoprostaglandin F1 alpha, thromboxane (TX) B2, prostaglandin (PG)E2, and PGF2 alpha, and in Tris buffer (pH 9.3) for determination of prostacyclin (PGI2)-like activity. No significant generation of TXB2, PGE2, or PGF2 alpha by rat aortic tissue could be detected. The time-dependent release of 6-keto-PGF1 alpha Krebs-Ringer bicarbonate buffer closely correlated with PGI2 generation in alkaline Tris buffer. During a 30-min incubation period, 6-keto-PGF1 alpha, release was 79.8 +/- 3.3 pmol/mg at a buffer potassium concentration of 3.9 mmol/liter and significantly increased by 23% to 98.3 +/- 8.5 pmol/mg (P less than 0.025) in the absence of potassium in the incubation medium. A smaller decrease in buffer potassium concentration to 2.1 mmol/liter and an increase to 8.8 mmol/liter did not significantly alter aortic 6-keto-PGF1 alpha release. Changes in the incubation buffer sodium concentration from 144 mmol/liter to either 138 or 150 mmol/liter at a constant potassium concentration of 3.9 mmol/liter did not alter the recovery of 6-keto-PGF1 alpha. Our results support the concept that PGI2 is the predominant product of arachidonic acid metabolism in rat aorta. They further show that PGI2 can be recovered quantitatively as 6-keto-PGF1 alpha under the present in vitro conditions. In addition, this in vitro study points to the potassium ion as a modulator of vascular PGI2 synthesis with a stimulation at low potassium concentrations.

Animals↗
PubMed1982

Prostaglandins participate in the regulation of NaCl absorption in the diluting segments of the nephron in vivo: effects of furosemide.

Various studies point to a role of the renal prostaglandin (PG) system in the regulation of renal NaCl excretion. In the present experiments, distal delivery of proximal tubular fluid (DD) [CH20 + CC1)/GFR x 100] and distal fractional chloride absorption (DFAC1) [CH20/(CH20 + CC1)] were studied in 6 healthy volunteers undergoing sustained water diuresis. Studies of renal function were performed during intravenous infusion of hypotonic (0.45%) saline and during additional treatment with indomethacin, furosemide and furosemide plus indomethacin. Hypotonic saline was infused at increasing rates of 0.09, 0.18, and 0.36 ml min-1 kg-1 body weight each for a 45-min period. DD over all three clearance periods averaged 8.27 +/- 0.71 ml min-1 100 ml-1 glomerular filtration rate (GFR) during saline infusion alone and was unchanged by indomethacin (8.09 +/- 0.63 ml min-1 100 ml-1 GFR). DFAC1 averaged 0.79 +/- 0.02 during saline and significantly increased to 0.87 +/- 0.01 (p less than 0.002) during concomitant indomethacin treatment. Increased NaCl absorption in the diluting segment during indomethacin was paralleled by a decrease in urinary excretion of chloride (UC1V) from 221 +/- 29 during control to 124 +/- 19 muEq/min (p less than 0.025) and in urinary excretion of PGE2 (UPGE2V) from 1.45 +/- 0.12 to 0.51 +/- 0.09 pmol/min (p less than 0.025). Furosemide increased UPGE2V to 2.94 +/- 0.34 pmol/min (p less than 0.05) and UC1V to 2,590 +/- 128 muEq/min (p less than 0.001). This effect was associated with an increase in DD to 26.70 +/- 1.33 ml min-1 100 ml-1 GFR (p less than 0.001) and a decrease in DFAC1 to 0.19 +/- 0.02 (p less than 0.001). Neither DD and DFAC1 nor UC1V were altered during furosemide+indomethacin as compared to furosemide in spite of a marked suppression of UPGE2V to 0.56 +/- 0.13 pmol/min. Our results support the concept that renal PG participate in the regulation of NaCl absorption in the diluting segments of the nephron. Furthermore, the tubular effects of furosemide appear not to be mediated by the PG system.

Absorption↗
PubMed1981

Natriuretic hormone - a circulating inhibitor of sodium- and potassium-activated adenosine triphosphatase. Its potential role in body fluid and blood pressure regulation.

Expansion of the extracellular fluid volume (ECFV) promotes the release of a small molecular weight (less than or equal to 1,000 Daltons) humoral natriuretic factor. The resulting natriuresis is accompanied by inhibition of renal cortical tissue and red blood cell Na-K-ATPase activity. This transport inhibitor, presumably an acidic peptide derived from a larger precursor molecule, was so far recovered from the serum and urine of rat, dog, and man, and from renal cortical tissue homogenate. Using Sephadex G-25 gel chromatography the inhibitor is eluted in the post-salt fraction IV. Its natriuretic action is demonstrated by bioassay methods, it depresses sodium transport of isolated amphibian membranes and inhibits Na-K-ATPase enzyme activity in vitro. The inhibitor isolated from human urine binds to specific antibodies against digoxin. This natriuretic factor is absent in patients with arterial hypotension and in edematous patients with secondary aldosteronism. In contrast, high inhibitory activity is found in patients with primary aldosteronism, a condition which represents the most classical type of low renin volume-dependent hypertension. Since enzyme inhibition by this humoral endogenous agent probably extends to various Na-K-ATPase-dependent transport systems including vascular smooth muscle fibers, depression of their Na-K pump will raise intracellular concentrations of sodium and calcium and thereby induce vasoconstriction. It is therefore tempting to speculate that the natriuretic hormone plays an important role in the pathogenesis of volume-dependent arterial hypertension.

Blood Pressure↗
PubMed1981

[Hepato-renal syndrome (author's transl)].

The hepato-renal syndrome is defined as potentially reversible functional renal failure associated with acute fulminant hepatitis or, more often, with advanced chronic liver failure. It is characterized by oliguria, azotemia, retention of sodium and water with formation of ascites, and hyponatremia. While urinary sodium concentration of less than 10 mEq/l reflects intact tubular sodium absorption, the kidney lacks the ability for adequate free-water generation. This condition must be separated from specific renal diseases which may arise during the course of intra-or extrahepatic diseases and which must be classified accordingly. Pathophysiological aspects of the hepa-to-renal syndrome include hemodynamic factors, such as changes in intrarenal blood flow distribution in the presence of elevated intrarenal and reduced peripheral vascular resistance. The functional relationship of vasoconstrictor, sodium retaining, and anti-diuretic hormones (e.g., renin-angiotensin, aldosterone, and vasopressin) to vasodilator, diuretic, and natriuretic hormonal factors (e.g., prostaglandins, kinins, and natriuretic hormone) may be altered as well. Finally, a pre- and intrahepatic spillover resulting in decreased endotoxin clearance must be considered. Due to the lack of understanding of their complex interactions, so far pharmacological and therapeutic approaches remained ineffective to correct at least some of these factors. Today, recovery from hepato-renal syndrome will, therefore, mainly depend on the course of the underlying liver disease.

Acute Kidney Injury↗
PubMed1981

Inner medullary osmolality and sodium concentration are decreased in rats during escape from DOCA-induced salt retention.

1. Papillary osmolality and sodium and potassium concentrations were determined in rats during a control period and during escape from the sodium-retaining effect of deoxycorticosterone acetate and compared with the changes observed after acute frusemide injection. 2. During escape, papillary osmolality [554 +/- 36 vs 754 +/- 42 mmol/kg of papillary water (H2O), P less than 0.005] and papillary sodium concentration (131 +/- 7 vs 182 +/- 8 mmol/kg H2O, P less than 0.001) were significantly decreased as compared with the control values, while papillary potassium concentration remained unchanged. 3. Frusemide decreased papillary osmolality to 538 +/- 41 mmol/kg H2O (P less than 0.005), papillary sodium concentration to 125 +/- 9 mmol/kg H2O (P less than 0.001) and papillary potassium concentration from 80 +/- 2 to 69 +/- 3 mmol/kg H2O (P less than 0.05). 4. The present results suggest that medullary portions of the distal tubule (probably the ascending loop of Henle) may represent one site of tubular sodium chloride rejection during escape from the sodium-retaining effect of deoxy-corticosterone acetate.

Animals↗
PubMed1981

Renal prostaglandins and water balance: studies in normal volunteer subjects and in patients with central diabetes insipidus.

1. In six healthy volunteer subjects polydipsic water loading significantly increased urine volume from 1203 +/- 242 (SEM) to 5072 +/- 320 ml/24 h (P less than 0.001) with a significant decrease in urinary osmolality. This increase in urine volume by more than fourfold was associated with a slight increase in urinary excretion of prostaglandin E2 from 466 +/- 66 to 1017 +/- 174 pmol/24 h (P = 0.05). 2. In five patients with central diabetes insipidus mean urine volume of 10 838 +/- 107 ml/24 h was reduced to 1205 +/- 204 ml/24 h (P less than 0.001) by treatment with 1-desamino-8-arginine vasopressin (desamino-[Arg8]vasopressin; 15 microgram/day) with a significant rise in urinary osmolality. Desamino-[Arg8]vasopressin treatment was associated with a significant increase of suppressed urinary excretion of prostaglandin E2 (PGE2) in four of these patients from 246 +/- 66 to 2643 +/- 677 pmol/24 h (P less than 0.01). 3. Concomitant treatment with indomethacin in addition to desamino-[Arg8]vasopressin significantly suppressed urinary excretion of PGE2 and significantly increased urinary osmolality as compared with treatment with desamino-[Arg8]vasopressin alone. 4. Desamino-[Arg8]vasopressin significantly increased urinary excretion of adenosine 3':5'-cyclic monophosphate (cyclic AMP). However, there was no further change in urinary excretion of cyclic AMP during concomitant indomethacin treatment. 5. The results suggest that urine flow itself is not an important determinant of urinary PGE2 excretion. In patients with central diabetes insipidus the urinary concentrating response to desamino-[Arg8]vasopressin is enhanced during inhibition of prostaglandin synthesis without changes in urinary excretion of cyclic AMP.

Adult↗
PubMed1981

Effects of triamterene and its phase I and phase II metabolities on sodium transport of the isolated frog skin.

We studied the effects of triamterene (TA) on its phase I and phase II metabolites, p-hydroxytriamterene (OH-TA) and p-hydroxytriamterene sulfuric acid ester (OH-TA ester), on sodium transport in the isolated frog skin. While TA applied to the inside (corial side) surface had no effects on potential difference (PD) and short-circuit current (SCC), TA, OH-TA, and OH-TA ester at a concentration of 10(-5) mol/l significantly decreased SCC by 19, 24 and 16%, respectively, when added to the solution bathing the outside (epithelial side) surface of the skin. In vasopressin-treated skins TA was more effective than OH-TA or OH-TA ester. In aldosterone-treated skins all compounds significantly suppressed SCC, the strongest effect was again exerted by TA. Only minor and transient changes in PD were noted. Inhibition of sodium transport was rapidly reversible when skins were washed with fresh Ringer solution. Thus, OH-TA and OH-TA ester possess qualitatively similar pharmacological activity as TA. The quantitatively smaller effects of OH-TA and OH-TA ester in the hormone-stimulated skin as compared to TA agrees well with their relative natriuretic potency observed in vivo.

Aldosterone↗
PubMed1980

Prostaglandin-independent protection by furosemide from oliguric ischemic renal failure in conscious rats.

In 38 conscious rats divided into seven groups, acute unilateral ischemic renal failure was induced by 1 hour of complete occlusion of the left renal artery while the contralateral kidney remained intact. Renal excretory function of the left kidney was monitored up to 144 hours after ischemia and revealed a typical course of oliguric renal failure with oligoanuria persisting for more than 48 hours. Urinary osmolality and sodium concentration became plasma isotonic after release of renal artery occlusion and approximated control values on day 6 after ischemia. In nine rats, the i.v. infusion of furosemide before (6 microgram/min/100 g body wt) and after (12 microgram/min/100 g body wt) renal artery occlusion protected the ischemic kidney from oligoanuria with endogenous creatinine clearance of 0.42 +/- 0.11 ml/min/g kidney wt 5 hours after ischemia. Tubular absorption of sodium and water was at least partially preserved 36 hours after ischemia when infusion of furosemide was stopped. The loop diuretic significantly (P less than 0.01) increased total urinary prostaglandin (PG) E2 excretion before and after renal artery occlusion; and 5 hours after ischemia, PGE2 excretion from the ischemic kidney significantly exceeded that from the intact kidney (P less than 0.05). Indomethacin (1 mg/100 g body wt) administered in six animals markedly suppressed control PGE2 excretion (P less than 0.05) as well as the furosemide-induced rise in urinary PG excretion before and after ischemia but did not modify the protective effect of the diuretic in this experimental model. Inhibition of PG synthesis, however, reduced urinary flow rate and sodium and potassium excretion of the contralateral intact kidney and almost completely prevented its compensatory rise in creatinine clearance. The results indicate that mechanisms other than the intrarenal prostaglandin system must be considered to mediate the protective effects of furosemide in acute ischemic renal failure.

Animals↗
PubMed1980

Immunoreactive substance P in human plasma: response to changes in posture and sodium balance.

1. In healthy volunteers plasma concentrations of immunoreactive substance P were measured in response to changes in posture and dietary salt intake. 2. In 14 subjects plasma immunoreactive substance P was 168 +/- 31 pmol/l when subjects were supine and 401 +/- 51 pmol/l (P less than 0.001) when they were ambulant. 3. Measurement of supine plasma immunoreactive substance P at 6 h intervals gave a mean value of 240 +/- 39 pmol/l at 14.00 hours and a lowest value of 76 +/- 9 pmol/l at 02.00 hours. 4. In eight healthy subjects plasma immunoreactive substance P rose only slightly from 169 +/0 41 pmol/l, on a sodium intake ad lib., to 244 +/- 45 pmol/l by day 4 of dietary sodium restriction (35 mmol/day) and significantly fell to 51 +/- 20 pmol/l (P less than 0.001) by day 4 of high sodium intake (350 mmol/day). 5. Although exogenous substance P was shown to be natriuretic in dog and rat, the present results do not favour a role of endogenous substance P as a circulating natriuretic factor in man.

Adult↗
PubMed1979

Effects of aprotinin on renal function and urinary prostaglandin excretion in conscious rats after acute salt loading.

1. Aprotinin, a potent kallikrein inhibitor, was given to conscious rats with and without expansion of the extracellular fluid volume with isotonic saline. 2. In non-expanded rats aprotinin had no effect on arterial pressure, glomerular filtration rate (GFR), hippuran clearance, urinary flow rate, absolute sodium and potassium excretion or free-water clearance. 3. In volume-expanded rats aprotinin significantly reduced GFR, hippuran clearance, urine volume (V) UNaV, UKV and Cwater/GFR without effect on systemic arterial pressure. 4. Urinary immunoreactive prostaglandin E2 excretion significantly increased during the expansion phase but returned to below the control range during stable extracellular fluid volume expansion. 5. Aprotinin significantly suppressed urinary immunoreactive prostaglandin E2 excretion in non-expanded rats and in volume-expand rats during the expansion phase, but not during stable expansion. 6. The results suggest that the kallikrein-kinin system may contribute to changes in renal function during extracellular volume expansion. This action may not necessarily be associated with changes in renal prostaglandin E2 activity.

Animals↗