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Biomedical subjects

H J Kramer

Publications and source records attributed to H J Kramer.

At least 109 records · Page 6Linked to original sources
PubMed1987

[Circulatory distribution of intravenously injected metallic mercury].

The mode of distribution and sites of deposition of mercury are discussed on the basis of the example of a 21-year old female nurse who had injected 4.5 ml of metallic mercury into her left cubital vein with suicidal intent, the findings being compared with the reports by 11 other authors. In particular, the influence of gravity on the distribution in the organism is emphasised. The proof of the decrease of an intrapulmonarily deposited amount of mercury within the observation period of 14 months furnishes ample evidence of the importance of a chronic absorptive mercury intoxication.

Adult↗
PubMed1986

Atrial natriuretic hormones--thirty years after the discovery of atrial volume receptors.

Twenty-five years after the discoveries of the existence of atrial granules and of volume receptors in the heart atria the search for natriuretic hormones has led to the isolation and identification of the atrial natriuretic factors (ANF) now considered as a hormonal system. These peptides are probably synthesized and stored in the Golgi apparatus of cardiac myocytes and are released in response to atrial wall stretch following acute plasma volume expansion and increased central blood volume, e.g., during head-out water immersion, in arterial hypertension, or increased left and/or right atrial pressure in cardiac failure, but also possibly in response to increased frequency of myocardial contractions, e.g. in paroxysmal tachycardia. The mechanisms of the renal action of these potent natriuretic hormones are not yet precisely known. Increased GFR may contribute to the initial rise in urinary sodium excretion and increased renal medullary blood flow to the later phase of natriuresis. The proximal tubule, the thin descending and the ascending limb of Henle's loop and especially the medullary collecting tubule were so far incriminated as tubular sites of action of ANF. Finally, recycling of sodium in medullary tissue and secretion of sodium via back-flux from the interstitium into the medullary collecting tubule are postulated to result in the hypernatric urine observed after ANF administration. Direct suppression of the secretion of renin, aldosterone, vasopressin, and vasopressin-stimulated cAMP synthesis may also contribute to its diuretic, natriuretic, and antihypertensive effects. The renal hemodynamic and tubular as well as the adrenal and systemic vascular effects are related to enhanced cGMP synthesis in medium-sized arterial vessels, in glomeruli and specific tubular segments, and in adrenal tissue, and may be calcium dependent. Specific ANF-binding sites were detected in these target organs. Although increased ANF release was observed in response to atrial distension in various disease states, which may contribute to renal sodium elimination in human hypertension and congestive heart failure, further studies are needed to identify its precise physiological and pathophysiological significance.

Amino Acid Sequence↗
PubMed1986

Converting enzyme inhibitor ramipril stimulates prostacyclin synthesis by isolated rat aorta: evidence for a kinin-dependent mechanism.

The present study was performed to investigate the effect of the angiotensin I-converting enzyme inhibitor ramipril on vascular synthesis of prostacyclin (PGI2). Administration of ramipril (Hoe 498) to rats significantly stimulated prostacyclin (PGI2) synthesis, quantified by radioimmunoassay of its stable hydrolysis product 6-keto-PGF1 alpha, by portions of the animals' isolated aorta. This effect was maximal at a dose range of 10(-7) mol/kg ramipril. The addition of the active ramipril metabolite ramipril diacid directly into the incubation buffer at final concentrations of 10(-9), 10(-6), and 10(-4) M resulted in a dose-dependent stimulation of 6-keto-PGF1 alpha released by isolated aortic tissue. Pretreatment of rats with aprotinin (40,000 U s.c. 60 min before the incubations) attenuated the ramipril-induced effect on aortic 6-keto-PGF1 alpha synthesis. Our results show that the angiotensin I-converting enzyme inhibitor ramipril stimulates PGI2 synthesis in vascular tissue and that this effect may be secondary to changes in the activity of the kinin system.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Effects of standard diuretics and RPH 2823 on transepithelial Na+ transport in isolated frog skin.

Short-circuit current (SCC) techniques were used to monitor the effects of various diuretic agents on Na+ transport in isolated frog skin, a model for the late distal tubule and the collecting duct of the mammalian kidney. Acetazolamide, hydrochlorothiazide, torasemide, and ethacrynic acid did not affect sodium transport (as indicated by the SCC) or transepithelial electrical resistance when added either to the apical (outer) or to the inner (basolateral, corial) bathing solution of the tissue. However, Na+ transport was sensitive to amiloride, the triamterene derivate dimethylamino-hydroxypropoxytriamterene (RPH 2823), and to furosemide. Whereas apical amiloride, and RPH 2823 induced a dose-dependent decrease in SCC and increase in transepithelial electrical resistance, apical furosemide resulted in a dose-dependent increase in SCC and a decrease in electrical resistance. None of the three diuretic agents caused a significant change in SCC when applied to the inner bathing Ringer's solution. The small furosemide-induced decrease in resistance compared with the huge increase in SCC suggests that furosemide affects Cl- permeability as well as Na+ permeability. Evidence for this notion was achieved by the following findings: The decrease in resistance after furosemide was more pronounced in tissues bathed in Cl(-)-free solutions compared with Cl(-)-containing solutions. n contrast, SCC stimulation by apical furosemide is Cl(-)-ion independent, but strongly Na+-ion dependent. SCC stimulation by furosemide is amiloride-sensitive. With respect to the onset, locus, and reversibility of action, it seems reasonable to assume that amiloride, RPH 2823, and furosemide all influence transepithelial Na+ transport by interacting with the Na+ channel or a regulator site of it within the apical membrane. The stoichiometry of the amiloride (RPH 2823)-receptor site interaction revealed Hill-coefficient(s) of less than 1, indicating a negative cooperativity among the receptor sites. The interaction between Na+ ions and amiloride or RPH 2823 displayed mixed competitive-noncompetitive inhibition. Taken together, these results support the hypothesis that amiloride and Na+ as well as RPH 2823 and Na+ may act at different loci on the apical entry mechanism in Rana esculenta skin.

Amiloride↗
PubMed1986

Studies on ouabain-like endogenous natriuretic factors in human urine. Inhibition of Na-K-ATPase and 3H-ouabain binding.

An endogenous inhibitor of sodium transport and of the Na-K-ATPase enzyme was previously detected in the small molecular weight postsalt fraction SIV of serum from saline-loaded rats after gel filtration on Sephadex G-25. In addition, a natriuretic factor present in this fraction of urine from salt-loaded subjects was found to bind to a specific digoxin antibody. Therefore, in the present study the small molecular weight natriuretic and digoxin antibody-binding activities present in the urine of salt-loaded healthy volunteers were purified by reverse-phase chromatography and by immunoprecipitation with the digoxin antibody and were studied for their in vitro effects on Na-K-ATPase derived from hog cerebral cortex. Na-K-ATPase inhibitory activities were found to roughly parallel the natriuretic activities at the various stages of purification. After reverse-phase chromatography, the material of fraction SIV which was bound to the digoxin antibody revealed the highest specific natriuretic activity of 3.95 +/- 0.29 mumol/min X mg injected material and showed strongest inhibition of the enzyme with I50 at a concentration of 0.08 microgram/ml, as compared with 2.4 micrograms/ml of the original postsalt urine fraction SIV. Fraction SIV revealed a noncompetitive inhibition of the enzyme with respect to potassium, but also significantly inhibited 3H-ouabain binding to the enzyme. Thus, the natriuretic substance(s) present in the urine of salt-loaded healthy subjects exhibit a potent inhibitory effect on the Na-K-ATPase enzyme which is similar, but not identical to that of ouabain.

Adult↗
PubMed1986

In vitro inhibition of Na-K-ATPase by trace metals: relation to renal and cardiovascular damage.

The potential role of trace metals in the pathogenesis of various disease states, especially of renal and cardiovascular disease, has been recognized increasingly. Moreover, altered membrane transport was recently incriminated to play a role in renal tubular syndromes, such as the Fanconi syndrome, as well as in the pathogenesis of volume dependent hypertension. We therefore investigated the possible in vitro effects of various trace metals on Na-K-ATPase, the biochemical correlate of active cellular transmembrane sodium and sodium-dependent transport. To more closely mimic the in vivo situation, we deliberately chose as enzyme source renal tissue homogenate, which may contain protective agents. Under these experimental conditions, the metals studied inhibited the enzyme quantitatively in the following order: Hg greater than Pb greater than Cd greater than Ur greater than Cu greater than Zn greater than Mn greater than Ba greater than Ni greater than Sr. Enzyme kinetic studies showed that Hg, Pb, and Cd competitively, and Cu noncompetitively, inhibited the enzyme. In general, Mg-ATPase was significantly less sensitive to the trace metals. Accumulation of these metals may present serious health hazards by producing a general defect in cell membrane transport. From the other metals studied, i.e., Mn, Ba, Ni and Sr, some may have toxic effects via other mechanisms, whereas some may exert a protective role against toxicity of other agents including metal ions.

Animals↗
PubMed1986

Studies on the tubular effects of atrial extract and of atriopeptin III in conscious rats.

To investigate a tubular action of atrial natriuretic peptide (ANP), in the present study the effects of rat atrial extract (AE) and of synthetic rat atriopeptin III (AP III) were assessed in conscious rats during hypotonic saline infusion. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were estimated by the clearances (C) of PAH and of endogenous creatinine, respectively. CPO4 was used as a marker of proximal tubular function. Distal delivery (DD) and distal fractional absorption of chloride (DFACl), a measure of solute absorption in the diluting segments, were calculated from CH2O and CCl. AE and AP III increased RPF in all groups of animals. Low doses of AP III (40 ng/100 g B.W.) significantly increased urine flow rate and CCl, whereas GFR, CNa, CPO4, and CK remained unaltered. The marked natriuresis at high doses of ANP was associated with a rise in GFR and in absolute and fractional CPO4 as well as an increase in DD and CK. AE and AP III (1 microgram/100 g B.W.) decreased DFACl from 0.94 +/- 0.03 and 0.87 +/- 0.03 to 0.80 +/- 0.07 (p less than 0.05) and 0.54 +/- 0.07 (p less than 0.01), respectively. Some of the effects on tubular reabsorptive capacity probably result from medullary wash-out which thereby contributes to the natriuresis by potentiating the rise in the filtered load of sodium at high ANP levels. In the absence of changes in GFR and CPO4, the tubular action of ANP is more accurately reflected by CCl which may result from decreased absorption in the medullary collecting tubule.

Animals↗
PubMed1985

[Mechanisms of postobstructive polyuria].

Postobstructive diuresis occurs after relief of bilateral ureteral obstruction despite the persistent decrease in renal cortical perfusion and glomerular filtration rate (GFR). After an initial transient rise in renal blood flow (RBF) during acute ureteral obstruction, tubular damage and progressive vasoconstriction with decreased RBF, especially of medullary perfusion, are observed with chronic obstruction. These are associated with an activation of the renin-angiotensin system and of renal prostaglandin (PG) synthesis with enhanced production of the vasoconstrictor thromboxane A2. Azotemia and extracellular fluid volume (ECFV) expansion result from impaired renal function. Mechanisms of polyuria following relief from bilateral chronic obstruction include enhanced PGE-mediated medullary blood flow, structural and functional tubular damage with decreased sodium reabsorption and (vasopressin-resistant) impaired renal concentrating ability, osmotic diuresis, activation of natriuretic factors following ECFV-expansion, and sometimes iatrogenic excessive fluid replacement. The resulting loss of fluid and electrolytes represents a major hazard in patients after surgical correction of congenital or acquired urinary tract obstruction.

Animals↗
PubMed1985

Excitation energy transfer in Rhodopseudomonas sphaeroides chromatophore membranes fused with liposomes.

The role of phospholipid in the structural organization of the light-harvesting complexes of Rhodopseudomonas sphaeroides was examined in photosynthetic (chromatophore) membrane vesicles fused with liposomes. Photochemically active preparations with progressive phospholipid enrichment up to greater than 15-fold were obtained by both polyethylene glycol- and acidic-pH-induced fusion. Their fluorescence emission at approximately 300 and 77 K was increased by 2-3.5-fold from the peripheral B800-850 antenna relative to that from the core B875 antenna. Up to 30-40% reduction in the efficiency of excitation energy transfer between B850 and B875 was also observed at 77 K suggesting a selective, phospholipid-induced dissociation of a portion of the B800-850 from the rest of the light-harvesting system.

Bacterial Chromatophores↗
PubMed1985

Studies on the role of sodium- and potassium-activated adenosine triphosphatase inhibition in the pathogenesis of human hypertension. Changes in vascular and cardiac function following inhibition of the sodium pump in normotensive subjects and effects of calcium entry blockade.

An endogenous humoral factor which inhibits the sodium- and potassium-activated adenosine triphosphatase (Na-K-ATPase) enzyme in vitro has been incriminated recently of playing a pathogenetic role in experimental and human hypertension. The present study was therefore performed in six healthy volunteers to investigate the hemodynamic consequences of an inhibition of this enzyme by ouabain, a potent and specific inhibitor of Na-K-ATPase. In addition, the role of intracellular calcium as a potential mediator was studied indirectly by the administration of nifedipine, a potent calcium entry blocker with predominant vasodilator properties. Intravenous administration of 8.5 micrograms ouabain/kg body weight inhibited red blood cell (RBC) - Na-K-ATPase by 49% which was accompanied by a significant increase in RBC - ATP and a decrease in intracellular potassium concentrations. This enzyme inhibition resulted in a 24% increase in peripheral vascular resistance. The parallel decrease in cardiac output and heart rate, however, prevented a rise in arterial pressure. This increase in vascular resistance was completely abolished by pretreatment with nifedipine (10 mg orally). In the absence of an effect of nifedipine on Na-K-ATPase, its attenuation of the vasoconstrictor effect of ouabain suggests that the effects of ouabain on the vascular smooth muscle cell are mediated by intracellular calcium. These results demonstrate that inhibition of the Na-K-ATPase enzyme in vivo causes a marked peripheral vasoconstriction. They are also compatible with the concept that an endogenous inhibitor of Na-K-ATPase - in the presence of decreased baroreceptor reflex sensitivity due to blood volume expansion - may play a role in the pathogenesis of human arterial hypertension.

Adenosine Triphosphate↗
PubMed1985

Effects of trifluoperazine and verapamil on the hydro-osmotic response to antidiuretic hormone in the urinary bladder of the toad.

To investigate the role of the intracellular calcium-calmodulin complex in the hydro-osmotic response to antidiuretic hormone (ADH), the effects of trifluoperazine (TFP), a well-established inhibitor of calmodulin-mediated functions, and of verapamil (V), a calcium entry blocker, were examined in the urinary bladder of the toad, a model for the late distal tubule and the collecting duct of the mammalian nephron. Preincubation of the hemibladders with TFP at serosal concentrations of 10(-5) and 10(-4) M was without effect on basal water flow but markedly reduced the maximal hydroosmotic response to ADH (50 mU/ml) in a dose-dependent manner as compared to control hemibladders (23.60 +/- 1.23 vs. 42.17 +/- 4.18 mg/min per hemibladder (10(-5) M TFP) and 5.43 +/- 0.59 vs. 52.50 +/- 4.67 mg/min per hemibladder (10(-4) M TFP). This inhibitory effect of TFP on the ADH-stimulated osmotic water flow persisted in the presence of naproxen (10(-5) M), a known inhibitor of prostaglandin synthesis. The hydro-osmotic response to cyclic adenosine 3',5' monophosphate (cAMP, 10(-3) M) was also significantly reduced in TFP-pretreated tissues (11.68 +/- 1.84 vs. 32.83 +/- 3.14 mg/min per hemibladder), suggesting a post-cAMP inhibitory effect of TFP. V (10(-4) M) had no effect on basal water flow but significantly reduced the hydro-osmotic effect of 50 mU/ml ADH (15.17 +/- 1.05 vs. 38.00 +/- 3.39 mg/min per hemibladder). In contrast, cAMP-stimulated osmotic water flow was significantly stimulated in V-treated tissues (48.07 +/- 1.95 vs. 27.13 +/- 1.50 mg/min per hemibladder).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Interaction of renal prostaglandins with the renin-angiotensin and renal adrenergic nervous systems in healthy subjects during dietary changes in sodium intake.

In six healthy subjects the role of renal prostaglandins (PG) in modulating the actions of the renin-angiotensin and renal adrenergic nervous systems on renal function was investigated. During high dietary sodium intake (350 mmol/day) for 4 days no changes in urinary excretion of PGE2, PGF2 alpha, noradrenaline or adrenaline were noted, whereas plasma renin activity (PRA) and urinary aldosterone excretion were suppressed. After 4 days of low sodium intake (35 mmol/day) urinary excretion of PGE2, aldosterone and noradrenaline, as well as PRA, had significantly increased. Inhibition of PG synthesis with indomethacin (2 mg/kg body weight) had no effects on renal function on day 5 of high sodium intake. Despite suppression of PRA and urinary aldosterone, indomethacin significantly reduced p-aminohippurate (PAH) clearance, glomerular filtration rate (GFR) and urinary sodium excretion on day 5 of low sodium intake, when urinary noradrenaline excretion remained high. The results point to the crucial role of the renal adrenergic nervous system in controlling renal vascular resistance and sodium conservation in healthy subjects during low sodium intake, which is unmasked when renal PG synthesis is blocked by indomethacin. Enhanced renal PG synthesis during sodium restriction therefore not only attenuates the vascular and tubular effects of the renin-angiotensin system but, more importantly, also those of the highly stimulated renal adrenergic nervous system.

Adult↗
PubMed1985

Effect of angiotensin II and captopril on renal tubular function in man.

The effects of nonpressor doses of intravenous angiotensin II and of the converting enzyme inhibitor captopril on renal excretory function were investigated in eight healthy volunteers during sustained water diuresis on a constant intake of 150 mmol sodium per day. The angiotensin II-analogue val5-angiotensin II-asp1-beta-amide was infused i.v. at an average dose of 2.6 ng kg-1 min-1 which was the highest dose without a significant effect on arterial blood pressure. This subpressor dose of angiotensin II significantly decreased urine volume, urinary excretion of sodium, chloride and phosphate and distal delivery [(CH2O + CCl)/GFR X 100] in the absence of changes in GFR or distal fractional chloride absorption [CH2O/(CH2O + CCl)]. In a second series of experiments, an oral dose of 50 mg of the angiotensin I-converting enzyme inhibitor captopril was given to the sodium replete volunteers. In this study, captopril did not affect arterial blood pressure, GFR or any of the determined parameters of renal tubular function. Our results strongly suggest that the nonpressor dose of angiotensin II induced renal retention of sodium chloride via increased absorption in the proximal tubule. Thus, they further support the concept that angiotensin II participates in the regulation of renal sodium chloride excretion by affecting proximal tubular absorptive capacity. However, in the sodium replete stage, angiotensin II is of no major importance in regulating sodium chloride excretion.

Adult↗
PubMed1985

Further characterization of the endogenous natriuretic and digoxin-like immunoreacting activities in human urine: effects of changes in sodium intake.

In the present study natriuretic activity and digoxin-like immunoreacting activity (DLIA) were determined in small molecular weight (MW) fractions of urine from healthy subjects during low (35 mmol/day) and high (greater than 400 mmol/day) sodium intake by bioassay and by a radioimmunoassay for digoxin, respectively. After gel filtration of urine on a Sephadex G-25 column the natriuretic activity appeared in the post-salt fraction SIV, whereas DLIA was present in small amounts in the salt fraction SIII and, with consistently higher activity, in the post-salt fraction SIV. Natriuretic activity significantly increased and DLIA decreased in fraction SIV with high sodium intake, but total urinary excretion of DLIA remained unaltered during changes in sodium intake. In addition, anion-exchange and reverse-phase chromatography revealed that DLIA is not specifically related to the natriuretic activity but also reflects unspecific binding of various urine constituents to this digoxin antibody. Although the antibody binds a natriuretic material, this radioimmunoassay is thus unsuitable to determine the endogenous natriuretic activity in urine fractions. Whereas they elute differently on reverse-phase chromatography, amino acid analyses revealed that both the natriuretic factor directly purified from the post-salt fraction SIV and the natriuretic material bound to the digoxin antibody have in common four amino acids at similar molar ratios. The physicochemical properties as evidenced by chromatographic and electrophoretic studies as well as enzymatic inactivation suggest that the low MW natriuretic factor(s) in human urine may be associated with a small peptide(s) of weak acidic nature.

Adult↗
PubMed1985

Digoxin-like immunoreacting substance(s) in the serum of patients with chronic uremia.

In patients with chronic uremia we have previously demonstrated a significant inhibition of the Na-K-ATPase enzyme which represents the specific receptor protein for cardiac glycosides. Since an endogenous inhibitor of this enzyme was previously shown to react with a digoxin antibody, in the present study we determined digoxin-like immunoreacting activity(ies) (DLIA) by a radioimmunoassay in 15 nondialyzed patients with chronic renal failure. In native serum, DLIA ranged from 0 to 1.70 ng/ml and was unrelated to the degree of renal failure. After gel filtration of serum, DLIA exclusively eluted in the small molecular weight salt (FIII) and post-salt (FIV) fractions and averaged 0.22 +/- 0.04 and 0.20 +/- 0.05 ng/ml in fractions III and IV, respectively. Total activities ranged from 0.11 to 0.88 ng/ml with a mean of 0.42 +/- 0.06 ng/ml and closely correlated with the degree of renal impairment (p less than 0.001). The results confirm the presence of small molecular weight digoxin-like immunoreacting substance(s) in uremic serum. The variable activities in native serum and the lack of correlation between the degree of renal failure and DLIA in serum fraction IV previously shown to possess the Na-K-ATPase-inhibiting activity, however, indicate that DLIA may not reflect specifically the endogenous sodium pump inhibitor and that unspecific binding to this digoxin antibody of uremic toxins or other endogenous compounds, such as steroids other than aldosterone, may have occurred.

Adult↗
PubMed1985

The role of endogenous inhibition of Na-K-ATPase in human hypertension--sodium pump activity as a determinant of peripheral vascular resistance.

High sodium intake in the presence of an intrinsic or acquired defect in renal sodium excretion will result in extracellular fluid volume (ECFV) expansion which is accompanied by decreased baroreceptor reflex sensitivity. We have shown that ECFV-expansion also stimulates the secretion of an endogenous inhibitor of the Na-K-ATPase enzyme and high activity of this sodium transport inhibitor was detected in plasma of patients with primary aldosteronism, the most classical type of volume-dependent hypertension. Thus, vasoconstriction due to inhibition of sodium pump activity of the vascular smooth muscle cell may contribute to the pathogenesis of human arterial hypertension. In analogy, ouabain (8.5 micrograms/kg) when administered i.v. to healthy volunteers inhibited RBC - Na-K-ATPase by 49% and significantly increased peripheral vascular resistance by 24 - 36%. The calcium entry blocker nifedipine (10 mg orally) completely prevented ouabain-induced vasoconstriction suggesting that the action of ouabain was mediated by a rise in intracellular calcium. High potassium intake partially abolished the vasoconstrictor effect of ouabain and also significantly increased baroreceptor reflex sensitivity. The results of these studies support the concept that inhibition of the sodium and potassium pump of vascular smooth muscle cells by a yet putative endogenous inhibitor of Na-K-ATPase (natriuretic hormone) may represent a crucial mechanism in the pathogenesis of at least certain forms of essential and secondary hypertension in man.

Animals↗