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Biomedical subjects

T J Rabelink

Publications and source records attributed to T J Rabelink.

At least 109 records · Page 6Linked to original sources
PubMed1995

Impaired endothelial function in patients with nephrotic range proteinuria.

Proteinuria is associated with increased cardiovascular morbidity and mortality. Release of nitric oxide by the endothelium has been advanced as an important defense mechanism against vessel-wall damage. In the present study we therefore tested the hypothesis that proteinuria is associated with a defect in nitric oxide-dependent vasodilation, by using venous occlusion plethysmography of the forearm in nine patients with nephrotic range proteinuria (> 3.5 g/24 hr) and normal renal function (creatinine 83.1 +/- 8.7 mumol/liter), eight patients with active glomerulonephritis but normal renal function (creatinine 81.2 +/- 5.4 mumol/liter) and low range proteinuria (< 1.0 g/24 hr), and ten healthy volunteers. We infused L-NMMA (2 mg/min) to inhibit basal nitric oxide production, serotonin (0.1, 0.3 and 1.0 ng/kg/min) as an endothelium-dependent vasodilator, and nitroprusside (1, 10, 30 and 100 ng/kg/min) as an endothelium-independent vasodilator into the brachial artery. Administration of L-NMMA decreased basal forearm vascular resistance (FVR) by 30 +/- 4% in the nephrotic subjects, 38 +/- 4% in the non-nephrotic patients and by 37 +/- 2% in the healthy controls (P = 0.15). Upon the highest dose of serotonin FVR decreased in nephrotic subjects by 40 +/- 5%, which was less than in non-nephrotic patients (56 +/- 3%; P < 0.05) or in healthy controls (55 +/- 3%; P < 0.05). The maximal decrease in FVR upon nitroprusside infusion was not different between the groups (respectively 84 +/- 2, 84 +/- 3 and 84 +/- 2%). The impaired serotonin-induced vasodilation could be attributed to a defect in nitric oxide production, since L-NMMA almost completely prevented serotonergic vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Naloxone inhibits renal hemodynamic effect of head-out water immersion in humans.

Head-out water immersion (HOI) is followed by renal vasodilation and natriuresis, in association with a fall in blood pressure. The latter suggests an exaggerated sympathetic suppression. We studied the role of endogenous opioids on the renal response to HOI. Six healthy subjects underwent four- hour clearance studies during: (1) time control; (2) naloxone 0.1 mg/kg i.v. bolus, followed by 0.1 mg/kg/hr; (3) HOI; and (4) concomitant HOI and naloxone administration. Compared to the time control study, naloxone had no effects on mean arterial pressure (MAP), plasma renin activity (PRA), aldosterone, catecholamines, atrial natriuretic peptide (ANP), glomerular filtration rate (GFR), estimated renal plasma flow (ERPF), and sodium excretion. HOI caused significant decrements of MAP, PRA, aldosterone, and catecholamines, and increased ANP, GFR, from 94 +/- 5 to 102 +/- 5 ml/min (P < 0.01), ERPF, from 529 +/- 30 to 616 +/- 35 ml/min (P < 0.01), and sodium excretion. Renal blood flow increased as well, and calculated renal vascular resistance decreased from 99 +/- 6 to 77 +/- 5 mm Hg.min.liter-1 (P < 0.01). HOI during concomitant naloxone administration had similar effects on MAP and humoral factors, however, caused no change in GFR, ERPF and renal blood flow, and the fall in renal vascular resistance, from 98 +/- 6 to 83 +/- 5 mm Hg.min.liter-1 (P < 0.05) was significantly less than found in the absence of naloxone (P < 0.05). The natriuretic effect was undisturbed. These data suggest that endogenous opioids play a role in the response to HOI, in particular, potentiate the renal vasodilatory response.

Adult↗
PubMed1995

Effectiveness of enalapril versus nifedipine to antagonize blood pressure and the renal response to endothelin in humans.

Endothelin-1 infusion into humans to obtain pathophysiological plasma levels causes mild hypertension, strong renal vasoconstriction, and sodium retention. We studied whether oral use of the angiotensin-converting enzyme inhibitor enalapril (20 mg BID) or the calcium channel blocker nifedipine (60 mg OD) could attenuate these effects of endothelin-1 (2.5 ng/kg per minute for 90 minutes) in six healthy volunteers. Endothelin infusion alone increased plasma endothelin from 3.0 +/- 0.3 to 8.8 +/- 1.0 pmol/L (P < .05). Blood pressure rose by approximately 6 mm Hg (P < .05). Renal function changes were relatively large: Renal blood flow decreased from 941 +/- 76 to 729 +/- 118 mL/min (P < .05) and glomerular filtration rate from 105 +/- 9 to 92 +/- 10 mL/min (P < .05); renal vascular resistance increased from 101 +/- 7 to 152 +/- 20 mm Hg.min/L (P < .05); and sodium excretion decreased from 158 +/- 54 to 86 +/- 27 mumol/min (P < .05). Enalapril treatment reduced blood pressure from 94 +/- 2 to 87 +/- 3 mm Hg (P < .05) and prevented the hypertensive response to endothelin. By contrast, despite renal predilatation, endothelin reduced renal blood flow strongly (from 1063 +/- 127 to 763 +/- 100 mL/min, P < .05), although maximal renal vascular resistance was numerically lower (124 +/- 11 mm Hg.min/L) than during endothelin alone (P < .05). Glomerular filtration rate fell from 118 +/- 11 to 108 +/- 11 mL/min (P < .05). Enalapril did not alter the antinatriuretic effect of endothelin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

High-flux dialysis membranes improve lipid profile in chronic hemodialysis patients.

In a controlled prospective trial, the effect of a switch from cellulose-based, low-flux dialysis membranes to polysulphone, high-flux membranes on lipid parameters was evaluated. Baseline values of lipid parameters were identical in the study group and the control group in which the dialysis membrane remained unchanged. After 6 wk, total triglyceride, very low-density lipoprotein (VLDL) triglyceride, and VLDL cholesterol decreased, respectively, 28 +/- 17 (P < 0.01), 38 +/- 17 (P < 0.01), and 24 +/- 21% (P < 0.05), and the proportion of total cholesterol that was high-density lipoprotein cholesterol increased from 15 +/- 5 to 18 +/- 5% (P < 0.05) in the high-flux polysulphone group, whereas these variables remained unchanged in the control group. Low-density lipoprotein and total cholesterol as well as Kt/V, protein catabolic rate, parathyroid hormone, albumin, and body weight did not change. No change in lipoprotein lipase activity was found. In a second study, the effects of a single hemodialysis session with high-flux polysulphone and low-flux, cellulose-based membranes on lipid parameters and lipolytic activity were compared in a cross-over fashion. Treatment with both membranes resulted in a significant decrease in plasma triglyceride, VLDL triglyceride, and VLDL cholesterol. Lipoprotein lipase activity increased during hemodialysis. Changes in lipid parameters and lipolytic activity were identical during the two treatments.

Adult↗
PubMed1995

Interactions of nifedipine with the renovascular effects of endothelin in humans.

Infusion of endothelin-1 in humans to obtain pathophysiological plasma levels causes mild hypertension, strong sodium retention and renal vasoconstriction. Animal studies have shown that part of these effects depend upon activation of voltage-dependent calcium channels. However, it is unknown whether hemodynamic effects of endothelin-1 in humans, once established, can be reversed by calcium channel blockers. We therefore studied in healthy subjects whether coinfusion of nifedipine, after 60 min of endothelin-1 infusion, could reverse these effects. During endothelin-1 infusion alone, plasma endothelin increased from 2.9 +/- 0.2 to 8.0 +/- 0.6 pmol/l (P < .05). Blood pressure rose by approximately 6 mm Hg at the end of the endothelin-1 infusion (P < .05). Endothelin-1 caused a marked increase in renal vascular resistance by approximately 34% (P < .05) and in filtration fraction by approximately 25% (P < .05). Sodium excretion decreased from a base-line value of 144 +/- 25 to 81 +/- 15 mumol/min at the end of the endothelin infusion (P < .05). During coinfusion of nifedipine, plasma endothelin levels increased to similar values as found during endothelin-1 infusion alone. Blood pressure increase was prevented, whereas the increase in renal vascular resistance and antinatriuresis were reversed completely. However, nifedipine could not reverse the endothelin-induced increase of filtration fraction, indicating that the effects of endothelin-1 and nifedipine in the renal microcirculation do not overlap completely. Because calcium channel blockers have a preferentially preglomerular effect, this suggests that endothelin-1 maintained vasoconstriction of the efferent arteriole in the kidney during nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Lipoprotein phospholipid composition and LCAT activity in nephrotic and analbuminemic rats.

Albumin is an acceptor of lysophosphatidylcholine (LPC), product of the lecithin:cholesterol acyl transferase (LCAT) reaction, and it has been suggested that low LCAT activity and reduced cholesterol esterification rate in patients with the nephrotic syndrome may be linked to depletion of albumin. Effects of low plasma albumin levels on LCAT activity, cholesterol esterification rates and LPC-binding were therefore studied in hyperlipidemic nephrotic (NS) and analbuminemic (NAR) rats. LPC-binding was also measured in normoalbuminemic rats with dietary hypercholesterolemia. Remarkably, LCAT activity, measured with excess exogenous substrate, was not decreased but increased in both NAR and NS rats. Molar esterification rates with endogenous substrate were increased in NAR but normal in NS rats. In normoalbuminemic rats, with or without hypercholesterolemia, LPC was primarily found in the lipoprotein-deficient plasma and the HDL3 fraction. In NAR and NS rats LPC levels were increased in lipoproteins (notably in LDL and HDL2), but, in marked contrast to normoalbuminemic rats, decreased in lipoprotein-deficient plasma. Phosphatidylcholine, quantitatively the major phospholipid, was distributed proportionally over the lipoproteins in NS, NAR and control rats. Therefore, in hypoalbuminemia and analbuminemia LPC is mainly bound to lipoproteins, which is in contrast to the paucity of LPC in these particles in normoalbuminemic rats. Cholesterol esterification in nephrotic plasma is thus not impaired by lack of an acceptor for LPC-binding. The absence of an increase in molar cholesterol esterification in conjunction with increased LCAT activity points to a possible defect of the substrate for this reaction in nephrotic plasma. Increased LPC levels in LDL, a characteristic of oxidized LDL, may be a hitherto unrecognized atherosclerotic risk factor in the nephrotic syndrome.

Animals↗
PubMed1994

Effects of endothelin-1 on renal function in humans: implications for physiology and pathophysiology.

Elevated levels of the vasocontrictor peptide endothelin-1 have been demonstrated in various pathological conditions that are characterized by sodium retention and/or renal vasoconstriction, such as heart failure, hepatorenal syndrome, renal failure and during administration of cyclosporin and radiocontrast. In the present study we studied in seven healthy subjects the renal and endocrine effects of systemic administration of endothelin-1 (0.5, 1.0 and 2.5 ng/kg/min). During endothelin-1 infusion plasma levels rose from 3.2 +/- 0.5 to respectively 5.0 +/- 0.8, 6.2 +/- 0.5 and 8.5 +/- 1.1 pmol/liter, values that can also be observed in physiological and pathological conditions. Infusion of low dosages of endothelin-1, that result in a twofold increase in plasma levels, decreased sodium excretion by 36%, without a significant effect on systemic and renal hemodynamics. Infusion of 2.5 ng/kg/min of endothelin-1 further enhanced sodium retention and, in addition, increased renal vascular resistance by 37%. Blood pressure did not change significantly. Pretreatment with the calcium channel blocker nifedipine caused renal vasodilation, which compensated for the renal vasocontriction by endothelin-1 and prevented sodium retention. Apparently, endothelin-1 participates in volume homeostasis in human, whereas pathophysiological concentrations can contribute to renal vasoconstriction and sodium retention. Calcium channel blockers may protect against these effects of endothelin-1.

Adult↗
PubMed1994

Arterial baroreflex control of renal hemodynamics in humans.

BACKGROUND: Control of renal hemodynamics by the arterial baroreflex has never been proved in humans. Apart from the physiological viewpoint, this issue is relevant because altered baroreflex function has been implicated in the pathogenesis of human hypertension. METHODS AND RESULTS: Renal function studies were performed in seated healthy volunteers (n = 12; age range, 20 to 34 years) during sustained neck suction at -60 mm Hg, aiming to selectively activate the carotid sinus arterial baroreceptors. Two protocols were followed. One group of 6 volunteers taking a 20 mmol/d sodium diet underwent 90 minutes of neck suction. Compared with a time-control study, neck suction decreased arterial pressure and heart rate; increased glomerular filtration rate (inulin clearance) from 104 +/- 6 to 114 +/- 8 mL/min (P < .01), renal plasma flow (para-aminohippurate clearance) from 616 +/- 52 to 665 +/- 42 mL/min (P < .01), and renal blood flow (from 1120 +/- 95 to 1209 +/- 77 mL/min, P < .01); and decreased renal vascular resistance (from 86 +/- 8 to 76 +/- 6 mm Hg.min.L-1, P < .01). Neck suction had no effect on plasma renin activity, aldosterone, atrial natriuretic peptide, catecholamines, and renal sodium excretion. The other 6 volunteers took a normal sodium diet and underwent sustained neck suction for 60 minutes. In this group, no effects on renal hemodynamics could be discerned, despite a modest decrease in blood pressure and heart rate. CONCLUSIONS: These data show, for the first time, that the arterial baroreflex is involved in the control of renal hemodynamics in humans. However, basal arterial baroreflex control of renal hemodynamics is probably low, and arterial baroreflex activation with subsequent renal vasorelaxation may be found only in conditions in which basal arterial baroreflex control of kidney function is significant, as is presumably the case in seated sodium-restricted subjects.

Adult↗
PubMed1994

Thrombus formation and platelet-vessel wall interaction in the nephrotic syndrome under flow conditions.

Increased in vitro platelet aggregability and hypercoagulability are generally held to be main determinants in the prethrombotic state in nephrosis. In vivo, however, thrombotic events depend on the dynamic interaction of flowing blood with the vessel wall. The present study confirms that aggregability of platelets of nephrotic patients is significantly increased by mere stirring or by exogenous stimuli as adenosine diphosphate and arachidonic acid. Moreover, the nephrotic patients have high von Willebrand factor and decreased red blood cell deformability, which normally increase platelet-vessel wall interaction. However, perfusion studies under well-defined flow conditions, in which anticoagulated nephrotic blood was exposed to deendothelialized human umbilical artery segments and sprayed collagen, showed normal platelet adhesion and only a modest increase in the deposition of platelet aggregates. This suggests that some factor counteracts platelet-vessel wall interaction under flow conditions in the nephrotic syndrome. When tissue factor associated with endothelial extracellular matrix (ECM) was allowed to generate thrombin, perfusions with nephrotic blood over this ECM resulted in a strong increase in fibrin generation. The capacity of patient blood to form increased amounts of fibrin appeared strongly correlated with the level of hyperfibrinogenemia. Platelet adhesion as well as aggregation in these experiments was even decreased below control values. This suggests that fibrin coverage may block the direct contact between blood platelets and matrix. We therefore also studied the isolated effect of high fibrinogen on platelet-vessel wall interaction by increasing fibrinogen concentrations in normal blood. Modulation of fibrinogen concentrations in normal blood could mimic all the observations in nephrotic blood: platelet aggregation in suspension increased with increasing concentrations of fibrinogen, while platelet adhesion and aggregate formation under flow conditions decreased. In perfusions over tissue factor-rich matrix, fibrin deposition increased. Therefore, our observations indicate that nephrotic hyperaggregability in suspension is not associated with increased platelet vessel wall-interaction under flow conditions. The latter is probably counteracted by high levels of fibrinogen. Our observations further suggest that hyperfibrinogenemia may be a major thrombotic risk factor in nephrosis by inducing more fibrin depositions.

Adenosine Diphosphate↗
PubMed1993

Role of glucocorticoid in excretion of an acute potassium load in patients with Addison's disease and panhypopituitarism.

Glucocorticoid (GC) has been shown to stimulate potassium (K) excretion in various conditions, but it is still incompletely resolved whether its presence is essential for the normal K homeostasis. We addressed this question in patients with selective GC deficiency (panhypopituitarism) and with combined GC and mineralocorticoid deficiency (Addison's disease), studied 24 hours after withdrawal of their regular substitution therapy. Compared to data in healthy subjects, both basal K excretion and the kaliuresis after a KCl load (1 mmol/kg body wt orally) were impaired in either patient group (P < 0.05). Physiological cortisol supplementation (20 mg 3 hr prior to test, and 1 mg/hr during test) increased basal K excretion (from 10.6 +/- 1.8 to 19.2 +/- 1.9 mmol/5 hr, P < 0.01) and KCl stimulated kaliuresis (from 47.9 +/- 6.1 to 54.8 +/- 4.7 mmol/5 hr, P = 0.06) to normal levels in panhypopituitarism. Cortisol also improved basal K excretion (from 10.2 +/- 1.5 to 16.9 +/- 3.5 mmol/5 hr, P < 0.05) and KCl-stimulated K excretion (from 31.6 +/- 2.5 to 45.2 +/- 3.8 mmol/5 hr, P < 0.05) in Addison's disease, although KCl-stimulated K excretion remained below normal (P < 0.01). The effects of cortisol on sodium excretion differed between the two patient groups (P < 0.05) in that only in Addison's disease the improved K excretion was associated with sodium retention. Additional experiments with the purely GC compound dexamethasone (0.5 mg 3 hr prior to test, and 0.03 mg/hr during test) in the patients with Addison's disease also improved K excretion (P < 0.05), but without the concomitant sodium retention observed after cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)

Addison Disease↗
PubMed1993

Iso-oncotic volume expansion in the nephrotic syndrome.

1. In previous studies we found that albumin infusions caused only a modest natriuresis in the nephrotic syndrome, suggesting that hypovolaemia played no part in the sodium retention of these patients. However, this finding was inconclusive, since the hyperoncocity of the infused albumin probably opposed sodium excretion. 2. In the present study, we examined the effect of sustained (68 h) plasma volume expansion (+18%), by means of iso-oncotic albumin infusions, on renal function, blood pressure, humoral factors and sodium balance. 3. Plasma atrial natriuretic peptide levels increased almost threefold and renin-angiotensin system activity was suppressed. Glomerular filtration rate remained unchanged, whereas estimated renal plasma flow increased, resulting in a further decrease in filtration fraction. 4. The increase in plasma volume expansion was accompanied by a modest increase in sodium excretion, which, however, was less than the amount of sodium daily infused with the albumin solutions and consumed with the diet, so that net sodium was retained. 5. This observation supports the concept that an intrinsic renal defect causes the sodium retention in the nephrotic syndrome, and argues against the therapeutic use of albumin infusions.

Adult↗
PubMed1993

Natriuretic response to head-out immersion in humans with recent kidney transplants.

1. Recently implanted kidneys may have decreased flexibility to adjust sodium excretion to volume challenges, since modulation by renal sympathetic nerve activity is absent. To examine this hypothesis, we studied the natriuretic response to head-out water immersion in eight patients with well-functioning renal allografts of 37 days (range 24-56 days), at a time when renal re-innervation has probably not occurred. 2. By the third hour of head-out water immersion, sodium excretion had increased equally in the patients (from 120 +/- 21 to 204 +/- 37 mumol/min) and in eight healthy control subjects (from 105 +/- 9 to 191 +/- 19 mumol/min). 3. Glomerular filtration rate was 60 +/- 6 ml/min in the patients and 113 +/- 6 ml/min in the control subjects, and did not change upon head-out water immersion. Estimated renal plasma flow increased upon head-out water immersion in the control group but not in the patients. Blood pressure decreased similarly in both groups. The renal vascular resistance, calculated from these data, decreased in response to head-out water immersion in the control subjects but not in the renal transplant patients. 4. Head-out water immersion suppressed plasma renin activity only in the normal group, whereas the plasma aldosterone level was suppressed in both groups. The natriuretic response in patients was associated with about 3-fold elevated plasma levels of atrial natriuretic peptide. 5. Since renal re-innervation at 37 days after transplantation is very unlikely, these data suggest that inact renal innervation is not mandatory for a normal natriuretic response to head-out water immersion in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Plasma volume regulation: defences against edema formation (with special emphasis on hypoproteinemia).

In hypoproteinemia, increased interstitial hydrostatic and decreased interstitial colloid osmotic pressures, together with increases in lymph flow, prevent interstitial fluid volume expansion, thus forming the edema-preventing mechanisms. Transfer of a substantial portion of the interstitial protein pool into the vascular compartment by increased lymph flow is the major edema-preventing mechanism. The increase in interstitial pressure during progressive interstitial fluid volume expansion is limited by the high compliance of the interstitium in most tissues. During hypoproteinemia low interstitial colloid osmotic pressure and high interstitial compliance permit augmented changes in plasma volume in response to rapid increases (orthostasis, venous constriction) and decreases (hemorrhage) in capillary pressure. Nevertheless, these same forces are responsible for the finding that during the relatively slow changes in sodium balance that occur during volume retention or after treatment with diuretics, the change in plasma volume is relatively small. These phenomena are illustrated by observations gathered in experimental hypoproteinemia and in patients with the nephrotic syndrome.

Animals↗
PubMed1993

Plasma lipoproteins and renal apolipoproteins in rats with chronic adriamycin nephrosis.

The relation between plasma lipoprotein composition and renal apolipoprotein deposition was studied in nephrotic rats in which stable renal function had been monitored for 7 months after a single low dose of adriamycin (ADR, 3 mg/kg). Proteinuria was observed 3 weeks after ADR and increased progressively up to about 0.5 g/day (versus 0.07 g/day in controls; P < 0.001), while the creatinine clearance remained stable at about 80% of control values. Hypercholesterolaemia was observed 6 weeks after ADR, and increased progressively up to 7.0 +/- 1.0 mmol/l (versus 2.3 +/- 0.1 mmol/l in controls; P < 0.001). Cholesterol was primarily located in LDL2 and HDL2 lipoproteins. Plasma apolipoprotein (apo) A-I increased by more than 400% in the nephrotic rats (P < 0.001). Apo B and apo E increased by about 60% (P < 0.01), whereas apo A-IV remained unchanged. Focal sclerotic lesions in glomeruli had an incidence of 50 +/- 10% in ADR rats versus 2 +/- 1% in controls (P < 0.001). Immunohistochemistry revealed apo A-I and apo A-IV in the visceral epithelium. Apo E immunoreactivity and lipid deposits were observed in focal glomerular sclerotic lesions of ADR rats. Neither apolipoproteins nor lipids were detected in glomeruli of controls. Proximal tubular localization of apolipoproteins was extensive for apo A-I, apo A-IV and apo E, but no differences were observed in tubular deposition of apolipoproteins between ADR and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of acute NaCl, KCl and KHCO3 loads on renal electrolyte excretion in humans.

1. Potassium salts increase sodium excretion in humans. To define the role of the potassium ion in this effect, we compared the effects of equimolar single oral loads of 100 mmol of NaCl and KCl on renal electrolyte excretion in seven healthy subjects. In a second group (n = 7), we infused equimolar loads of NaCl or KCl (0.75 mmol/kg in 2 h). 2. In both experiments the KCl load quickly increased plasma potassium and aldosterone concentrations and potassium and sodium excretion to a maximum by 2 h after the load, whereas the NaCl load had no such effect. 3. In a third group (n = 7) we compared the effects of single oral loads of KCl and KHCO3 (1 mmol/kg), to assess the role of the anion in the natriuretic effect of potassium salts. 4. KCl and KHCO3 transiently stimulated urinary excretion of potassium and sodium in an identical manner. 5. We also followed the changes in acid excretion over time. Whereas both KCl and KHCO3 loading decreased acid excretion, this effect was greater after KHCO3 loading. Interestingly, acid excretion did not decrease further after the first collection hour after the potassium load, although the plasma potassium concentration was still increasing. 6. From these data we conclude (1) that increased excretion of sodium, potassium and chloride and decreased excretion of protons after administration of potassium salts are the specific effects of the potassium component; (2) that potassium also appears to have secondary, indirect effects on proton excretion, the mechanism of which remains to be clarified.

Administration, Oral↗
PubMed1991

Sodium retention by insulin may depend on decreased plasma potassium.

Evidence is accumulating that insulin is a hypertensive factor in humans. The involved mechanism may be its sodium-retaining effect. We examined whether insulin causes sodium retention through a direct action on the kidney, as is generally assumed, or indirectly through hypokalemia. Insulin was infused (euglycemic clamp technique) with and without potassium infusion to prevent hypokalemia in six healthy subjects. Without potassium infusion, insulin caused a marked decrease in plasma potassium (-0.75 mmol/L), and decreased urinary sodium and potassium excretions by, approximately 38% and 65%, respectively. Simultaneous potassium infusion largely prevented the decrease in plasma potassium, as well as the decrease in urinary sodium and potassium excretions. These data suggest that the acute antinatriuretic effect of insulin may be largely mediated in an indirect way, ie, through hypokalemia.

Adult↗
PubMed1991

Role of prostaglandins in the natriuresis of head-out water immersion in humans.

1. Prostaglandins may play a role in the natriuresis seen after acute circulatory challenges. To assess this role in head-out water immersion, we compared, in clearance studies, the effects of acute (24 h) and chronic (7 days) administration of indomethacin, an inhibitor of prostaglandin synthesis, on the renal response to head-out water immersion in six healthy subjects on a 200 mmol of sodium/day diet and on a 40 mmol of sodium/day diet. 2. Indomethacin caused a similar degree of sodium retention on each of these two diets. 3. During the 40 mmol of sodium/day diet, acute administration of indomethacin decreased sodium excretion before, as well as during, head-out water immersion; however, the relative increase caused by head-out water immersion was normal. After chronic administration of indomethacin, both baseline sodium excretion and the natriuresis induced by head-out water immersion were similar to those in control studies. 4. During the 200 mmol of sodium/day diet, indomethacin had no effect on baseline sodium excretion, nor on the natriuretic effect of head-out water immersion. 5. Head-out water immersion decreased tubular lithium reabsorption and increased diluting segment delivery. Despite opposite effects of indomethacin on these parameters, indomethacin did not prevent the tubular effects of head-out water immersion on either diet. However, indomethacin did prevent the marked increase in estimated renal plasma flow and the fall in filtration fraction that were observed during head-out water immersion in the absence of indomethacin (control). 6. Head-out water immersion was not associated with an increase in urinary excretion of prostaglandins.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗