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Biomedical subjects

H J Kramer

Publications and source records attributed to H J Kramer.

At least 127 records · Page 7Linked to original sources
PubMed1985

Relation of endogenous digoxin-like immunoreacting activities to salt balance and renal function in man.

We have previously shown that a natriuretic factor which is present in a small molecular weight fraction (IV) of serum and urine from salt loaded animals and healthy subjects, respectively, inhibits the Na-K-ATPase enzyme in vitro and also binds to a specific digoxin antibody. In the present study digoxin-like immunoreacting activity (DLIA) was therefore determined in the serum of healthy volunteers during low (35 nmol/day) and high (greater than 400 mmol/day) sodium intake and of patients with chronic renal failure and serum creatinine concentrations ranging from 127 to 757 mumol/l. DLIA was determined with a radioimmunoassay for digoxin in native serum and in the salt (III) and post-salt (IV) serum fractions eluted from a Sephadex G-25 column. DLIA in native serum of healthy subjects was less than 0.125 ng/ml. After gel filtration DLIA eluted exclusively in the small molecular weight salt (F III) and post-salt (F IV) fractions. Whereas DLIA increased in F III and decreased in F IV, total DLIA in F III + IV slightly increased from 0.37 +/- 0.03 to 0.49 +/- 0.05 ng/ml (p less than 0.01) with the change from low to high sodium intake. DLIA in native serum of uremic patients ranged from 0 to 1.70 ng/ml and was detectable consistently only in patients with serum creatinine concentrations above 250 mumol/l. DLIA in F III which averaged 0.22 +/- 0.04 ng/ml and total activity which ranged from 0.11 to 0.88 ng/ml closely correlated with the degree of renal impairment (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Further studies on the mechanism of increased blood pressure during dietary linoleic acid deprivation.

The present studies investigate the changes in blood pressure and excretory renal function in rats during dietary linoleic acid deprivation. Four groups of animals were fed isocaloric diets containing 10 en % saturated fat and either 5 en % linoleic acid (groups I and III) or 5 en % oleic acid (groups II and IV). In addition, groups I and II received a chronic high intake of Na (greater than 5 mmol/day) while groups III and IV were Na restricted with an average Na intake of 0.7 mumol/day. Blood pressure significantly increased in the high salt, linoleic acid deprived group II and was unchanged in all three other groups of animals. De novo synthesis of prostaglandin E2 in rat kidney inner medullary homogenates in the four groups of animals at the end of the dietary protocol showed a marked dependency on Na balance with significantly (p less than 0.01) higher values in the Na restricted animals as well as on linoleic acid intake with significantly (p less than 0.01) higher values in the linoleic acid substituted animals. Urinary excretion of NaCl during acute expansion of the extracellular fluid volume with hypotonic saline was significantly impaired in the animals receiving oleic acid instead of linoleic acid. In a metabolic study, linoleic acid deprived animals retained Na from the first day of linoleic acid deprivation and blood pressure started to rise only after a substantial amount of Na had been retained. Our results show that linoleic acid deprivation suppresses renal arachidonic acid cyclooxygenase metabolism and impairs the renal ability to excrete an acute salt load. Impaired renal excretory function precedes the increase in blood pressure. Thus suppressed renal cyclo-oxygenase metabolism which impairs renal excretory function may be a crucial mechanism in the rise of blood pressure during dietary linoleic acid deprivation.

Animals↗
PubMed1983

The converting enzyme inhibitor captopril stimulates prostacyclin synthesis by isolated rat aorta.

In the present study, pretreatment of rats with captopril significantly stimulated prostacyclin (PGI2) synthesis by their isolated aorta. This effect was maximal at captopril doses of 1.0 mumol/kg body weight. When added directly into the incubation buffer, captopril at final concentrations of 50 and 500 nM also increased the synthesis of PGI2 by isolated rat aorta. Our results show that captopril stimulates PGI2 synthesis in vascular tissue and that this effect may be due at least in part to a direct action of this substance.

Angiotensin I↗
PubMed1983

Interaction of bemetizide and indomethacin in the kidney.

The effect of a single oral dose of 25 mg bemetizide on renal function without and with concomitant administration of the prostaglandin synthesis inhibitor indomethacin was investigated in ten healthy volunteers during sustained water diuresis. Bemetizide induced a significant increase in urinary sodium and chloride excretion from 196 +/- 30 and 163 +/- 28 mumol/min to 690 +/- 54 and 537 +/- 51 mumol/min (P less than 0.01). This effect occurred in the absence of changes in glomerular filtration rate, urinary excretion of phosphate or the delivery of chloride beyond the proximal nephron to the distal tubules (distal delivery) [(CH2O + CCl)/GFR . 100], but was associated with a significant decrease in distal fractional chloride absorption (DFACl) [CH2O/(CH2O + CCl)] from 0.84 +/- 0.02 to 0.63 +/- 0.02 (P less than 0.01). Bemetizide also increased urinary excretion of prostaglandin (PG) E2. Concomitant indomethacin administration significantly suppressed urinary excretion of PGE2 and markedly decreased urinary excretion of sodium and chloride during control and following bemetizide administration. Indomethacin had no effect on glomerular filtration rate, urinary excretion of phosphate, distal delivery or the urinary excretion of bemetizide but significantly increased DFACl both during control and after bemetizide administration. Our results show that bemetizide as a thiazide-diuretic acts in the diluting segments of the nephron. Indomethacin administration induces retention of sodium and chloride and blunts the renal effects of bemetizide via increased absorption in the diluting segments. The interaction of both drugs most likely represents a pharmacodynamic interaction.

Adult↗
PubMed1983

Dietary linoleic acid deprivation: effects on blood pressure and PGI2 synthesis.

The possible role of arachidonic acid metabolites in the regulation of arterial blood pressure was investigated in rats receiving 0, 5, or 9 energy (en) % linoleic acid in their diet (groups 1-3) over 6 wk. In group 1 animals, systolic arterial blood pressure significantly increased from 100.5 +/- 2.0 to 110.6 +/- 3.1 mmHg (P less than 0.01) after 6 wk of dietary linoleic acid deprivation, whereas no effect on blood pressure was observed in group 2 and 3 animals receiving dietary linoleic acid supplements. Generation of prostacyclin (PGI2)-like activity by isolated aorta from rats fed the different diets was determined using a platelet-aggregation bioassay following incubation of aortic tissue for 12, 15, and 30 min, respectively. In isolated aorta from rats fed the 5 en% linoleic acid, production of PGI2 was 55.9 +/- 1.2, 70.5 +/- 2.6, and 90.9 +/- 3.6 pmol/mg over the three incubation periods. In group 1 animals, a significant suppression of PGI2 generation to 35.4 +/- 1.5, 41.1 +/- 1.7, and 55.0 +/- 1.2 pmol/mg (P less than 0.005) was observed, whereas PGI2 production was unaltered in aortic tissue from group 3 animals. In contrast, plasma concentrations of circulating thromboxane B2 were highest in group 1 animals (2.15 +/- 0.38 pmol/ml) and measured 1.28 +/- 0.17 and 0.83 +/- 0.10 pmol/ml in group 2 and 3 animals, respectively. Our results demonstrate that dietary deprivation of the arachidonic acid precursor linoleic acid increases arterial blood pressure that is associated with a suppression of vascular PGI2 synthesis and, most likely, a secondary rise in circulating thromboxane concentrations.

Animals↗
PubMed1983

Substance P-induced changes in kidney function in the conscious rat: relation to the renal prostaglandin system.

Infusion of substance P into the renal artery was previously shown to cause a significant natriuresis which was associated with increased kallikrein excretion. Since the renal kinin and prostaglandin (PG) systems may be interrelated, the present study was performed to investigate the effects of substance P on renal function and its potential interaction with the renal PG system in the conscious rat. 24 female Sprague-Dawley rats were infused intravenously with substance P (1 ng . min-1 . kg-1 body weight) and the body weight was kept constant by an intravenous infusion of 0.45% saline. Substance P had no effects on arterial blood pressure, glomerular filtration rate (GFR) and 125I-hippuran clearance in the absence or presence of indomethacin (INDO). Basal UPGE2 V was unaltered by substance P infusion but was suppressed by INDO before and during substance P by 80 and 88%, respectively. Substance P raised urinary flow rate (V) by 105%, CH2O by 96%, UNaV by 378%, UKV by 48% and UPO4V by 147% (p less than 0.001). Although INDO significantly suppressed V, CH2O, and UNaV during all collection periods, it did not affect absolute UPO4V and UKV and the relative rise in V, CH2O, and UNaV induced by substance P. Thus, the diuretic and natriuretic effects of substance P are not mediated by renal PG, but are partially blunted by INDO through increased distal absorption of sodium and water, INDO has no effect on substance P-induced alterations in proximal tubular function.

Animals↗
PubMed1983

Renal functional and metabolic studies on the role of preventive measures in experimental acute ischemic renal failure.

In the present study 1 h of total occlusion of the left renal artery in conscious rats was chosen as experimental model of ischemic acute renal failure (ARF), while the contralateral kidney was left intact. Chronic high dietary sodium intake, acute isotonic saline infusion, or administration of saralasin did not protect from ARF. Furosemide, mannitol, and verapamil converted oliguric into non-oliguric ARF in 100%, 75%, and 60% of the animals, resp. Protection from oliguria and preservation of GFR inversely correlated with the depression of cortical ATP-concentration (control: 1.32 +/- 0.07 mumoles/g wet weight) 6 h after ischemia by 16%, 41%, and 58% in mannitol- and verapamil- treated rats and in untreated rats, resp. At this time, Na-K-ATPase enzyme activities in renal cortex and papilla were unaffected, while enzyme activity in outer medulla was suppressed from 15.4 +/- 1.4 to 9.4 +/- 1.0 mumoles Pi/mg protein h in all groups of animals. The results suggest that in this model of ARF renal ischemia not only affects cellular energy supply in renal cortex but also causes severe structural and functional impairment in the outer medulla, probably leading to tubular obstruction and depression of glomerular function. Pharmacological protection from ischemic oliguric ARF cannot be achieved by prior induction of high urine flow rates alone but depends on the degree of metabolic and functional reserve of the injured tubular epithelium.

Acute Kidney Injury↗
PubMed1983

Studies on the oxygen toxicity after administration of chelate-forming agents in mice.

The influence of the chelating agents CaNa2-EDTA, penicillamine, dimercaprol, unithiol, dithiocarb, aurin tricarboxylic acid, salicylic acid, and acetylsalicylic acid on the toxicity of oxygen at elevated tension was studied in mice. With the possible exception of dimercaprol, no increase in toxic effects of oxygen was observed after administering these chelate-forming agents in the doses used.

Animals↗
PubMed1983

Interaction of the kinin and prostaglandin systems in mediating renal function and intrarenal hemodynamics.

The roles of the renal kinin and prostaglandin (PG) systems were indirectly assessed in conscious rats by inhibition of PG synthesis with indomethacin (INDO) and of kinin synthesis with aprotinin (APRO). In control animals APRO and INDO had no effect on urine flow, Na and K excretion, GFR, RPF or arterial pressure. Both inhibitors, however, significantly depressed renal PG synthesis and deep cortical and medullary plasma flow. Acute saline loading was achieved by i.v. 0.9% NaCl to increase body weight by 10%. APRO and INDO decreased urine flow and Na and K excretion to a similar degree which was highly significant as compared to saline loading in the absence of APRO or INDO. The decrease in RPF following APRO and INDO during saline loading was completely due to a decrease in outer cortical perfusion. APRO suppressed the early rise in PGE2 excretion during saline loading. The similar effects of inhibition of kinin- and PG-synthesis on renal function support the concept that both systems are closely interrelated. The present results also suggest that the integrity of the kinin and PG systems represents an important prerequisite for appropriate vascular and natriuretic responses of the kidney to an acute isotonic saline load.

Animals↗
PubMed1982

Hemodynamic and hormonal responses to 8-arginine-vasopressin in healthy man: effects of indomethacin.

Previous investigations suggest that in a normotensive organism the vasopressor effect of 8-arginine-vasopressin (AVP) is very effectively buffered by cardiovascular reflex mechanisms. Exogenous AVP administration shows only small, transient increases in blood pressure in spite of continued AVP-infusion and high plasma AVP concentrations. The present study aims to clarify the mechanism of the observed transient blood pressure elevations which are often referred to as "tachyphylaxis". Our results in healthy subjects show a two phase response to exogenous AVP: an initial phase which is characterized by cardiac reflex mechanisms and a second phase during which a normalisation of the elevated total peripheral resistance occurs. Inhibition of prostaglandin synthesis with indomethacin almost completely attenuates this vascular counterregulation to exogenous AVP, thus providing evidence that a prostaglandin mediated vasodilation in response to AVP may be the underlying mechanism for "vasopressin tachyphylaxis". The role of the renin-angiotensin-system and the importance of different regional hemodynamic effects of AVP are discussed.

Adult↗