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T J Rabelink

Publications and source records attributed to T J Rabelink.

119 records · Page 7Linked to original sources

Early and late adjustment to potassium loading in humans.

We studied the adaptation to early (72 hr) and late (20 days) K loading (400 mmol/day, 4 equal meals every 6 hour) in six healthy humans. Throughout the study, each single K meal was followed by an acute transient rise in plasma K, aldosterone and kaliuresis. "K balance" (urinary K excretion approximately 80% of intake) was achieved in the second 24 hour period of K loading. This was associated with elevated plasma K and aldosterone, slightly negative sodium (Na) balance and stimulated plasma renin activity. At 20 days of K loading Na loss had been compensated. Plasma renin activity and aldosterone had returned to baseline, although the latter kept increasing after each single K meal. Compared to the first K meal, the K meals at 72 hours and 20 days of K loading were followed by more kaliuresis, while the natriuretic effect had disappeared. Abrupt discontinuation of K loading was followed by negative K balance, lasting only 24 hour, and by Na retention, lasting 72 hours. In conclusion, switching to a high K diet in humans is immediately followed by increased renal K excretion, and by Na loss. K excretion increases over a few days, while Na loss is halted. This can be explained by the rise in plasma aldosterone, secondary to elevated plasma K and renin activity. After weeks, renal adaptation forms an additional factor promoting K excretion and preventing natriuresis. The latter appears specifically from the Na retention which occurs after discontinuation of K loading in the absence of persistent aldosterone stimulation.

Adaptation, Physiological↗

Effects of atrial natriuretic peptide on distal tubule function in humans.

To characterize the actions of atrial natriuretic peptide (ANP) in the human distal nephron, we studied interactions between ANP (0.02 micrograms/kg.min i.v.) and acutely administered substances acting in the distal nephron, that is, amiloride and aldosterone, in six healthy humans during maximal water diuresis. ANP increased NaCl excretion, fractional lithium excretion (FELi) and decreased diluting segment reabsorption estimated from free water clearance. Amiloride increased natriuresis, had no effect on FELi, but decreased diluting segment reabsorption. Aldosterone had the opposite effect. When infused in addition to amiloride, ANP still increased NaCl excretion, the changes in sodium handling parameters being comparable to those seen after ANP alone. Amiloride did not increase the further natriuretic response to ANP. These findings suggest that ANP increases distal sodium delivery, and decreases sodium reabsorption in distal segments by a mechanism also sensitive to amiloride. ANP abolished much of the antinatriuretic effect of aldosterone, which may also be explained by assuming a partial overlap of the target segments of ANP and aldosterone in the distal nephron. Remarkably, in neither of these experiments was the natriuresis after ANP accompanied by a kaliuresis, for which the explanation remains obscure.

Adult↗

Blunted natriuretic response and low blood pressure after atrial natriuretic factor in early cirrhosis.

We compared the natriuretic response to a standard dose of atrial natriuretic factor in nine patients with early cirrhosis (no ascites or edema) with the response in normal subjects displaying a range of baseline sodium excretions due to different sodium intakes (20 mmoles per day, n = 9; 100 mmoles per day, n = 9, and 200 mmoles per day, n = 9). In these normal subjects, sodium output rose, in the same order, from 49 +/- 12 to 177 +/- 26, from 116 +/- 21 to 365 +/- 106 and from 228 +/- 29 to 901 +/- 85 mumoles per min in the first 20 min after 100 micrograms atrial natriuretic factor (human atrial natriuretic factor 99-126). Thus, irrespective of basal excretion, natriuresis rose by at least 2-fold. In the cirrhotic patients, natriuresis rose from 173 +/- 42 to 305 +/- 77 mumoles per min, that is by hardly 1-fold, significantly less than in the normal subjects (p less than 0.01). Renal function studies indicated that atrial natriuretic factor caused less rise in glomerular filtration rate and in fractional sodium excretion. Atrial natriuretic factor induced a fall in blood pressure only in the cirrhotic group, from 130 +/- 4/81 +/- 2 to 108 +/- 4/68 +/- 3 mmHg (p less than 0.001). Plasma atrial natriuretic factor was not low in the cirrhotic patients. Although these data are compatible with a primary disturbance of sodium excretion in early cirrhosis without ascites, such an explanation is complicated by the concomitant drop in blood pressure after atrial natriuretic factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Role of ANP in natriuresis of head-out immersion in humans.

Atrial natriuretic peptide (ANP) may play a role in the natriuresis after acute circulatory challenges. To assess this role in head-out water immersion (HOI), we compared in clearance studies the effect of 3 h HOI with an equally natriuretic 3-h infusion of ANP [0.01 microgram.kg-1.min-1 human ANP-(99-126)] in seven healthy individuals taking a 100 mmol sodium diet. The studies were repeated after treatment with enalapril (20 mg twice daily), which in previous studies inhibited the natriuresis after ANP. HOI caused a natriuresis equal to that of ANP infusion despite an about five times smaller rise in plasma ANP. HOI increased and ANP decreased estimated renal plasma flow (ERPF). HOI increased maximal free water clearance and decreased fractional lithium reabsorption. ANP did not affect these variables but raised minimal urine osmolality. Enalapril enhanced the fall in ERPF caused by ANP and abolished its natriuretic effect; enalapril did not impair either the natriuresis after HOI or the increase in ERPF and the fall in lithium reabsorption. These data indicate that the low dosage of ANP causes natriuresis by reducing sodium absorption in a distal nephron target segment; enalapril impairs this effect, perhaps by enhancing ANP-induced vasoconstriction, which decreases delivery to this target segment. HOI, by increasing sodium delivery to this segment, is natriuretic despite only a small rise in plasma ANP. Enalapril does not impair these effects. Although a rise in plasma ANP may be one factor in the natriuresis of HOI, the present data speak against an exclusive role. Other factors determine the magnitude of the natriuretic response.

Adult↗

Pitfalls of venous occlusion method for determination of capillary pressure in humans.

We tested the method of estimating capillary pressure from venous pressure transients obtained after sudden venous clamping in a hydrodynamic model. The basic principles were confirmed in the model, but it was found that when occlusion was caused over a relatively wide distance or in a predistended vessel, capillary pressure was overrated. This problem was due to volume backflow from the occlusion site, since it could be eliminated by placing a one-way valve upstream from the occlusion site. Upstream from the valve, the venous pressure transient accurately followed capillary pressure. Downstream, however, the reading of capillary pressure was impaired by the backflow volume squeezed between valve and occlusion clamp, which caused an immediate large pressure elevation. We also tested the method recently advanced to estimate capillary pressure in humans from venous pressure curves obtained after rapid venous occlusion with an air-filled compression cuff. With the cuff around the upper arm, venous pressure was recorded at different levels along the forearm. The tracings obtained from the dorsum of the hand and halfway along the forearm did not show the initial rapid upstrokes that might indicate the capillary pressure. Tracings obtained slightly below or above the cubital fossa were similar to those seen downstream from the one-way valve in the model. Extrapolation to zero-time, using the distally recorded curves as a template, yielded values equal to venous pressure. We conclude that although the problem of backflow can be circumvented by pressure recording distal from venous valves, the method of venous occlusion by a circular upper-arm cuff may not be appropriate to estimate capillary pressure in humans.

Blood Pressure Determination↗

Lithium clearance in water immersion-induced natriuresis in humans.

Lithium clearance (CLi) has been advanced as a measure of sodium delivery from the proximal tubules. Because information on the intrarenal effects of water immersion is only limited, and available data are conflicting with respect to the effects on the proximal tubule, we examined the effects of 3 h of water immersion on renal functional parameters, including CLi, in eight healthy subjects. Studies were carried out during maximal water diuresis. Water immersion resulted in a significant increase in sodium excretion, from preimmersion values of 74.0 +/- 9.6 to 155.4 +/- 12.0 mumol/min at the third immersion hour (P less than 0.01). This natriuresis was accompanied by an increase in CLi from 26.3 +/- 1.9 (preimmersion) to 37.0 +/- 3.1 ml/min (P less than 0.01). Fractional lithium reabsorption (FRLi) decreased from 76.4 +/- 1.0 to 69.6 +/- 1.3% (P less than 0.01). None of these changes was found in eight healthy subjects undergoing a time-control study without water immersion. The large fall in FRLi found during immersion is compatible with a major resetting of the proximal glomerulotubular balance. In this regard the renal response to water immersion resembles saline expansion rather than mere intravascular expansion. The lithium data suggested a large rise in distal delivery accompanied by an almost as large rise in distal reabsorption. The free water clearance data were in agreement with this interpretation. However, no changes were found in fractional excretion of phosphate and uric acid. Therefore such a major resetting of proximal glomerulotubular balance can be doubted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Opposite effects of enalapril and nitrendipine on natriuretic response to atrial natriuretic factor. Renal function evaluated with clearance studies in humans.

In clearance studies, we analyzed the effect of Ca2+ entry blockade with nitrendipine treatment (20 mg b.i.d. for 4 days) and of converting enzyme inhibition with enalapril treatment (20 mg b.i.d. for 4 days) on renal response to atrial natriuretic factor (ANF) (25 micrograms bolus followed by an infusion of 0.03 microgram/kg/min for 90 minutes) in six healthy volunteers who were taking 300 mmol sodium daily. In a control study ANF was administered without Ca2+ entry blockade or converting enzyme inhibition. Natriuresis rose from 239 +/- 38 to 605 +/- 137 mumol/min in the control study (p less than 0.05), from 330 +/- 53 to 943 +/- 152 mumol/min with Ca2+ entry blockade (p less than 0.05), and from 236 +/- 22 to 344 +/- 39 mumol/min with converting enzyme inhibition (NS). ANF induced a rise in maximal free water clearance, inulin clearance, and in the excretion of multiple electrolytes except potassium. Fractional lithium reabsorption fell. In general, these effects were stronger during Ca2+ entry blockade and blunted during converting enzyme inhibition. p-Aminohippurate clearance tended to decrease during the control study (NS), remained constant during Ca2+ entry blockade, and decreased significantly when ANF was infused during converting enzyme inhibition (p less than 0.05 vs. control and vs. Ca2+ entry blockade study). Blood pressure was lowered by Ca2+ entry blockade and, to a somewhat greater extent, by converting enzyme inhibition, but ANF administration induced no additional fall except for a short-term drop during Ca2+ entry blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Enhanced natriuretic effect of atrial natriuretic factor during mineralocorticoid escape in humans.

We examined the question of whether escape from the sodium-retaining effect of mineralocorticoid involves an increased natriuretic effect of atrial natriuretic factor (ANF). Seven healthy volunteers taking a 170 mmol Na/100 mmol K diet received an intravenous bolus (25 micrograms) followed by a 1-hour infusion (0.02 micrograms/kg/min) of ANF (human ANF-[99-126]) before and after 10 days of 9-fludrocortisone acetate, 0.5 mg b.i.d. Escape was accompanied by an increase in body weight (from 72.2 +/- 12.9 to 74.0 +/- 12.6 kg; p less than 0.05), mean arterial pressure (from 95 +/- 4 to 109 +/- 3 mm Hg; p less than 0.01), plasma ANF (from 9 +/- 2 to 24 +/- 4 pmol/L; p less than 0.01), and inulin clearance (from 124 +/- 9 to 137 +/- 7 ml/min; p less than 0.05). Indexes for renal sodium handling (lithium and free water clearance) were compatible with a decreased "proximal" and an increased "distal" tubular reabsorption fraction. ANF infusion raised inulin clearance comparably before and after escape to 138 +/- 10 and 152 +/- 7 ml/min, respectively, but the natriuretic effect was much larger (p less than 0.05) after escape (from 366 +/- 34 to 1294 +/- 278 mumol/min) than before (from 248 +/- 48 to 630 +/- 124 mumol/min). Indexes for tubular reabsorption were consistent with greater suppression of both "proximal" and "distal" tubular sodium reabsorption by ANF after versus before mineralocorticoid expansion. These results indicate that escape is accompanied not only by a rise in plasma ANF but also by potentiation of the natriuretic effect of ANF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Endothelin and its antagonists in hypertension: can we foresee the future?

Endothelin-receptor antagonists may soon become a new therapeutic class of agents used to treat cardiovascular diseases. Although the first clinical trials are anxiously awaited to position this new family of compounds in the treatment of essential or secondary forms of hypertension, we dispose of an impressive amount of studies in which plasma endothelin levels have been measured, in addition to chronic preclinical studies that provide a general picture of what we can expect from these drugs. The experimental models that do respond to endothelin- receptor antagonists share vascular overexpression of endothelin, which seems directly linked with vascular hypertrophy of resistance arteries. In addition, salt sensitivity may represent an unbalanced condition between relaxing and constrictive properties of the renal endothelium that can respond favorably to endothelin blockade. Thus, African-American hypertensives may well be a responsive target population for the new drugs. In addition to blood pressure control, endothelin may also be involved in the evolution of end-organ damage by its potent vasoactive and vasoproliferative properties. The kidney, heart, large arteries and brain may therefore benefit from these drugs, but it is still unclear if this benefit goes beyond what can be attributed to the reduction of arterial pressure. Moreover, most studies performed so far have looked at prevention of end-organ damage, while very few have addressed the clinically relevant question of regression of lesions already installed by the disease process.

Antihypertensive Agents↗

The benefit of STent placement and blood pressure and lipid-lowering for the prevention of progression of renal dysfunction caused by Atherosclerotic ostial stenosis of the Renal artery. The STAR-study: rationale and study design.

BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) is associated with progressive loss of renal function and is one of the most important causes of renal failure in the elderly. Current treatment includes restoration of the renal arterial lumen by endovascular stent placement. However, this treatment only affects damage caused by ARAS due to the stenosis and ensuing post-stenotic ischemia. ARAS patients have severe general vascular disease. Atherosclerosis and hypertension can also damage the kidney parenchyma causing renal failure. Medical treatment focuses on the latter. Lipid-lowering drugs (statins) could reduce renal failure progression and could reduce the overall high cardiovascular risk. The additional effect on preserving renal function of stent placement as compared to medical therapy alone is unknown. Therefore, the STAR-study aims to compare the effects of renal artery stent placement together with medication vs. medication alone on renal function in ARAS patients. METHOD: Patients with an ARAS of > or = 50% and renal failure (creatinine (Cr) clearance < 80 mL/min/1.73 m2) are randomly assigned to stent placement with medication or to medication alone. Medication consists of statins, anti-hypertensive drugs and antiplatelet therapy. Patients are followed for 2 yrs with extended follow-up to 5 yrs. The primary outcome of this study is a reduction in Cr clearance > 20% compared to baseline. This trial will include 140 patients.

Angioplasty, Balloon↗