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Biomedical subjects

D de Zeeuw

Publications and source records attributed to D de Zeeuw.

At least 163 records · Page 9Linked to original sources
PubMed1989

Atrial natriuretic peptide-induced decreases in renal blood flow in man: implications for the natriuretic mechanism.

1. We studied the effect of a low-dose infusion of atrial natriuretic peptide (ANP) on renal blood flow in healthy volunteers. We additionally investigated the effect of ANP on renal haemodynamic function and on urinary sodium excretion. 2. ANP induced a rise in packed cell volume and a slight increase (but no decrease) in the renal extraction of hippuran. These changes did not offset the observed fall in effective renal plasma flow. Renal blood flow thus truly decreased and renal vascular resistance increased. 3. ANP induced an increase in glomerular filtration rate and a decrease in urinary osmolality in the first hour of ANP infusion, whereas absolute and fractional sodium excretion increased significantly only in the second hour of ANP infusion. The decrease in urinary osmolality in the first hour of ANP infusion correlated with the induced natriuresis. The changes in urinary osmolality and sodium excretion both correlated with the changes in plasma ANP levels. 4. These data indicate that ANP may cause a decrease in renal blood flow and an increase of renal vascular resistance in man. Our results suggest a role for ANP-induced (intra)renal haemodynamic changes in ANP-induced natriuresis, possibly through an increase in the filtered load of sodium into a washed-out medullary interstitium.

Adult↗
PubMed1989

Antihypertensive effect of a 5-day infusion of atrial natriuretic factor in humans.

Atrial natriuretic factor was infused in a low dose (0.2 microgram/min) during 5 days in six patients with essential hypertension. Atrial natriuretic factor infusion caused plasma levels of atrial natriuretic factor to increase from 49 +/- 10 to 106 +/- 19 pg/ml. Within 4 hours after the start of the atrial natriuretic factor infusion, urinary sodium excretion increased in all subjects. Sodium balance was regained after 24 hours with a net loss of 72.3 +/- 14.6 mmol. However, systolic as well as diastolic blood pressure started to decrease gradually in all subjects only after 12 hours of atrial natriuretic factor infusion, reaching a stable level after 36 hours with a decrease of 11.5 +/- 1.5% and 10.3 +/- 0.8%, respectively. Heart rate increased in parallel by 12.6 +/- 3.1%. Hematocrit rose 7.1 +/- 2.3%. After cessation of atrial natriuretic factor infusion, plasma atrial natriuretic factor levels, sodium balance, and hematocrit returned to baseline within 24 hours, whereas blood pressure slowly returned toward baseline values over 3 days. These data show that chronic atrial natriuretic factor infusion in patients with essential hypertension causes a negative sodium balance and a rise in hematocrit, followed by a smooth decrease in blood pressure with a rise in heart rate until a new equilibrium is reached after approximately 2 days. Thus, atrial natriuretic factor in low doses appears intimately involved in the regulation of sodium balance and blood pressure in humans. Moreover, these data suggest that atrial natriuretic factor-like substances will eventually become useful antihypertensive drugs.

Antihypertensive Agents↗
PubMed1989

Diagnostic use of angiotensin converting enzyme inhibitors in radioisotope evaluation of unilateral renal artery stenosis.

Iodine-123 hippurate renography, [99mTc]diethylenetriaminepentaacetic acid (DTPA) renography, and [99mTc]dimercapto succinic acid (DMSA) renal scintigraphy were performed before and during angiotensin converting enzyme (ACE) inhibition in a group of 15 hypertensive patients with angiographically "significant" unilateral renal artery stenosis. Visual and quantitative evaluation of the three radioisotope methods before ACE inhibition already disclosed abnormalities suggestive of renal artery stenosis in a high percentage (87%, 60%, and 60%, respectively) in this group of patients, but ACE inhibition further improved the diagnostic yield in all three methods (93%, 86%, and 80%). Iodine-123 hippurate renography was at least as useful as [99mTc]DTPA renography in this respect, while [99mTc]DMSA scintigraphy can be used particularly in segmental stenosis. Despite a large drop in blood pressure after ACE inhibition little adverse reactions were seen and overall renal function was fairly well maintained, the exceptions noted in patients with initially a more impaired renal function.

Adolescent↗
PubMed1989

Renal handling of technetium-99m DMSA: evidence for glomerular filtration and peritubular uptake.

The finding of an enhanced excretion of [99mTc]dimercaptosuccinic acid (DMSA) in patients with tubular reabsorption disorders prompted us to investigate the role of filtration in the renal handling of [99mTc]DMSA. Our studies in human serum indicated that binding to serum proteins was approximately 90%. Chromatography of human urine and studies in rats showed that the complex was excreted unaltered into the urine. Renal extraction of [99mTc]DMSA in a human volunteer was 5.8%. Continuous infusion of [99mTc]DMSA in 13 individuals with normal renal function gave the following results (mean +/- s.d.): plasma clearance of [99mTc]DMSA 34 +/- 4 ml/min, urinary clearance of [99mTc]DMSA 12 +/- 3 ml/min. The calculated filtered load of [99mTc]DMSA closely resembled the urinary clearance, whereas the plasma clearance was about three times faster. This indicates that peritubular uptake accounts for approximately 65% and filtration for approximately 35% of the renal handling of [99mTc]DMSA.

Animals↗
PubMed1988

A new constrictor device for external induction of a long-term stable and irreversible renal artery stenosis in the dog.

A new externally adjustable constrictor device for renal artery stenosis in the dog is described. The constrictor combines hydraulic and mechanical characteristics, and is connected to the exterior of the animal by a thin catheter. Applying hydraulic pressure via the catheter causes the plunger in the device to compress the renal artery to any desired degree of stenosis. A mechanical catch prevents backward movement of the plunger, thus ensuring a stable, irreversible renal artery constriction. This constrictor was implanted in 13 dogs, together with an electromagnetic blood flow sensor around a renal artery. In twelve dogs the constriction procedure was performed 3-12 weeks after implantation, and in all 12 cases the intended degree of stenosis [defined as percentage renal blood flow reduction (RBF)] was achieved within a range of 10%. In 5 dogs the long-term stability of the stenosis was studied and the RBF reduction appeared to be stable up to at least 6 weeks after constriction. In conclusion, the presented constrictor device is easily externally adjustable, and allows induction of a stable renal artery stenosis of various degrees in the conscious dog.

Animals↗
PubMed1988

Micro-HPLC and transfer techniques for directly measuring drug (indomethacin) transport across the isolated perfused renal proximal straight tubule.

We wished to study the active transport of indomethacin across isolated segments of renal proximal tubules. To do so, we developed a microbore HPLC technique capable of directly measuring pharmacologic concentrations of indomethacin in nanoliter sample volumes. The technique also required development of methods for transferring of samples, introduction of internal standard and identification of an oil, under which the sample could be collected without interference with the assay itself or the compounds of interest. We found that gamma-terpinene could be used as the oil, for it did not impede the assay, did not dissolve indomethacin or inulin, and indomethacin and inulin remained stable in the water phase. Transfer of sample was effected with a glass tube containing 640 nL of water plus internal standard into which the indomethacin sample pipette (110 nL) could be introduced. This transfer tube was then capped with PE-60 tubing, which could later be used for withdrawing sample into an injection syringe for HPLC assay. This method proved feasible for measuring indomethacin transport across isolated perfused proximal tubule segments and should be applicable for similar studies of other drugs.

Animals↗
PubMed1988

Angiotensin converting enzyme inhibition induces alterations to hippuran renography despite unchanged ipsilateral renal blood flow in conscious two-kidney, one clip Goldblatt hypertensive dogs.

We performed experiments in the two-kidney, one clip Goldblatt hypertensive dog to see whether angiotensin converting enzyme (ACE) inhibition could improve the sensitivity of hippurate renography in detecting renal artery stenosis. Ten dogs on a sodium-restricted diet were studied before and after induction of a renal artery stenosis. In the absence of renal artery stenosis nine dogs showed normal renograms before ACE inhibition, and one was false positive. During ACE inhibition all 10 renograms were normal. With a renal artery stenosis 50% of the renograms were false negative, whereas a 100% sensitivity was reached during ACE inhibition. The alterations induced by the ACE inhibition on the renograms were not related to changes in renal blood flow. In conclusion, ACE inhibition markedly improved the sensitivity of hippurate renography in the two-kidney, one clip dog.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Is the antiproteinuric effect of dipyridamole hemodynamically mediated?

We studied the acute antiproteinuric and renal hemodynamic effect of dipyridamole 30-60 mg intravenously in 13 salt-depleted patients with the nephrotic syndrome of different etiology. Whereas mean arterial pressure did not change, a small fall in glomerular filtration rate with a concomitant fall in filtration fraction and a decrease in urinary protein loss occurred. The fall in filtration fraction was positively correlated with the fall in proteinuria. This suggests that the antiproteinuric effect of dipyridamole is at least partly due to an efferent vasodilation with a fall in intraglomerular capillary pressure.

Dipyridamole↗
PubMed1988

Angiotensin converting enzyme inhibition improves diagnostic procedures for renovascular hypertension in dogs.

In renovascular hypertension adaptive mechanisms in the poststenotic kidney are a probable cause of the 20 to 25% false-negative findings during rapid sequence urography or [123I]o-iodohippurate renography. We blocked the renin-angiotensin system in an effort to increase the yield of these diagnostic procedures. Chronically instrumented, salt-depleted conscious dogs were used in which a light (n = 5), moderate (n = 4), or severe (n = 2) renal artery stenosis was induced. Before stenosis 10 of the dogs showed no left-right differences with either diagnostic procedure, and angiotensin converting enzyme (ACE) inhibition did not change this result. Two to 3 weeks after induction of a renal artery stenosis, all dogs showed signs of renovascular hypertension. However, only 50% of the renograms and 22% of the urograms showed differences between the two kidneys indicative of the presence of stenosis. After ACE inhibition, all previously negative test results became positive (abnormal) and previously existing left-right differences became more evidence. Electromagnetically measured renal blood flow on the stenotic side did not change during ACE inhibition (146 +/- 13 vs 145 +/- 21 ml/min), whereas contralateral blood flow showed a distinct increase (207 +/- 18 vs 282 +/- 20 ml/min, p less than 0.01). In conclusion, ACE inhibition markedly improves the sensitivity of rapid sequence urography and hippurate renography in the diagnosis of renovascular hypertension in the two-kidney, one clip Goldblatt hypertensive dog. The effects of ACE inhibition on the handling of the different tracers do not appear to be related to its effects on renal blood flow or systemic blood pressure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Indomethacin secretion in the isolated perfused proximal straight rabbit tubule. Evidence for two parallel transport mechanisms.

We studied indomethacin as a probe of anion transport across the isolated perfused proximal straight tubule of the rabbit and discovered that a substantial component of transport may occur by anion exchange at the basolateral membrane. Various perturbations involving direct or indirect dissipation of the cellular sodium gradient (ouabain, sodium- or potassium-free solutions, cooling to 18 degrees C) resulted in only a 50% inhibition of indomethacin transport, which raised the question of a co-existent alternative pathway for secretion. Similarly, the anion exchange inhibitor, 4,4'-diisothiocyanostilbene (DIDS), diminished indomethacin secretion by only 50%. Cooling followed by DIDS or the reverse sequence resulted in additive inhibition such that the combination abolished active secretion of indomethacin. We conclude that active secretion of indomethacin by the proximal straight tubule appears to be in part sodium gradient dependent; the remainder may be driven by an anion exchanger on the basolateral membrane.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1987

Reduction of proteinuria by angiotensin converting enzyme inhibition.

The effects of the angiotensin converting enzyme (ACE) inhibitor lisinopril on blood pressure, proteinuria and renal hemodynamics were evaluated in 13 patients with renal disease of different origin. A comparison was made with the effects of conventional antihypertensive therapy. Both drug regimens significantly lowered blood pressure, while only after 12 weeks of treatment with lisinopril, blood pressure was significantly lower than during conventional therapy. Lisinopril reduced proteinuria (by 61 +/- 40%), whereas conventional therapy had no significant effect on protein excretion. During the first eight weeks of treatment with lisinopril, there was a comparable degree of blood pressure reduction with both treatment regimens, whereas urinary protein loss was significantly less during ACE inhibition. There was only a nearly-significant positive correlation between the fall in proteinuria during lisinopril and the concomitant decrease in mean arterial pressure. Glomerular filtration rate decreased from 26.3 +/- 11.6 to 20.6 +/- 9.4 ml/min during treatment with lisinopril. This decrease was not correlated with the fall in proteinuria. A significant positive correlation existed between the fall in urinary protein excretion and both the decrease in overall renal vascular resistance, and the fall in filtration fraction. Although blood pressure lowering by itself could contribute to the antiproteinuric effect of lisinopril, our results suggest that this effect of ACE inhibition is also due to efferent (postglomerular) vasodilation. We conclude that the ACE inhibitor lisinopril effectively reduces blood pressure and proteinuria in renal disease. The latter effect is not only the result of a lower blood pressure, but is probably also due to a fall in intraglomerular capillary pressure.

Adult↗
PubMed1987

Moderate sodium restriction in hypertensive subjects: renal effects of ACE-inhibition.

It has been suggested that AII-mediated renal mechanisms limit the efficacy of moderate sodium restriction in the lowering of blood pressure (BP) in hypertension. We therefore studied renal hemodynamics and sodium handling in nine essential hypertensives in balance on 200 and on a 50 mmol sodium diet, before and during ACE-inhibition (enalapril 10 mg bid for 8 days) in a cross-over fashion. BP was similar on 50 and 200 mmol Na before enalapril, the fall in BP during enalapril was significantly more pronounced on 50 mmol Na. On 50 mmol Na, GFR and filtered Na were significantly lower, and tubular reabsorption was significantly higher than on 200 mmol Na. GFR increased during enalapril in 50 but not on 200 mmol Na. Consequently, the differences in GFR and filtered load elicited by sodium restriction were no longer present during ACE-inhibition. In contrast, the differences in tubular reabsorption between 50 and 200 mmol Na persisted during enalapril. In conclusion, moderate sodium restriction, not affecting BP, can elicit a renal hemodynamic response. As this response is blunted by ACE-inhibition it is probably mediated by AII. This blunting may contribute to the increased sodium sensitivity of BP during ACE-inhibition. The adaptation of tubular sodium reabsorption is not affected by ACE-inhibition.

Adult↗
PubMed1987

Diuretic effects of angiotensin-converting enzyme inhibition: comparison of low and liberal sodium diet in hypertensive patients.

Inhibitors of the angiotensin-converting enzyme (ACE) acutely increase sodium excretion. Whether or not continued treatment induces net negative sodium balance is not clear, and may depend on initial sodium balance. We therefore investigated the effects of 8 days of treatment with enalapril, 10 mg b.i.d., on sodium balance in 10 subjects with uncomplicated essential hypertension, in balance on a low (50 mmol sodium/24 h) and a liberal (200 mmol sodium/24 h) sodium intake. Sodium excretion exceeded intake during the first days of treatment, amounting to sodium losses of 101 +/- 24 and 112 +/- 15 mmol in the low and the liberal sodium diets, respectively. The sodium loss was accompanied by a fall in body weight with both regimens. The blood pressure response to enalapril was potentiated by the sodium-restricted diet. The net increase in sodium excretion after enalapril administration, however, was similar for both diets. This was particularly true for individual patients, suggesting an individual response pattern to ACE inhibition.

Adult↗
PubMed1986

Effects of nonsteroidal anti-inflammatory drugs on proteinuria.

Most nonsteroidal anti-inflammatory drugs are anti-proteinuric agents, especially if the patient is sodium-depleted. The decline in urinary protein excretion induced by these agents always markedly exceeds the decrease in glomerular filtration rate. Moreover, the remaining proteinuria appears to be more selective. Together, these findings suggest that the anti-proteinuric effect of nonsteroidal anti-inflammatory drugs is hemodynamically mediated. Nonsteroidal anti-inflammatory agents that reduce renal prostaglandin E2 excretion also decrease proteinuria, whereas sulindac decreases neither prostaglandin E2 nor protein excretion. In a retrospective study, it appeared that administration of indomethacin improved renal survival of nephrotic patients with an initial serum creatinine concentration of less than 110 mumol/liter. The anti-proteinuric effect of indomethacin itself or indomethacin-induced hemodynamic changes might explain this observation.

Anti-Inflammatory Agents↗
PubMed1986

Effect of human atrial natriuretic peptide on blood pressure after sodium depletion in essential hypertension.

Human atrial natriuretic peptide was infused over four hours in three patients with essential hypertension. When the patients had a sodium intake of 200 mmol (mEq) daily an infusion of 0.5 micrograms atrial natriuretic peptide/min caused no significant change in blood pressure, whereas an infusion of 1.0 micrograms/min caused a gradual decrease in blood pressure and an increase in heart rate. After two to three hours of infusion with the higher dose two patients showed a sudden decrease in heart rate, with symptomatic hypotension. When the same patients had an intake of 50 mmol sodium daily their blood pressure was more sensitive to infusion of atrial natriuretic peptide; one patient again developed symptomatic hypotension, this time during an infusion of 0.5 micrograms/min. During all infusions distinct natriuresis occurred irrespective of whether blood pressure was affected. Prolonged, relatively low dose infusions of atrial natriuretic peptide can cause unwanted symptomatic hypotension. The effect on blood pressure is enhanced after sodium depletion, and blood pressure should be monitored carefully during longer infusions of atrial natriuretic peptide in patients with essential hypertension.

Adult↗