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Biomedical subjects

D de Zeeuw

Publications and source records attributed to D de Zeeuw.

188 records · Page 11Linked to original sources

Effects of enalapril on blood pressure and renal haemodynamics in essential hypertension.

The effects of enalapril were assessed in a double-blind study versus propranolol. Twenty-two patients with essential hypertension were titrated with either enalapril (5, 10 and 20 mg twice daily) or propranolol (40, 80 and 120 mg twice daily). With propranolol blood pressure decreased from 154/101 +/- 4/1 to 146/98 +/- 5/2 mmHg (mean +/- SEM); with enalapril it decreased from 151/103 +/- 3/1 to 134/92 +/- 4/2 mmHg, both after 12 weeks of therapy. Effective renal plasma flow remained unchanged in the propranolol group whereas it increased from 413 +/- 19 to 445 +/- 27 ml/min (p less than 0.05) with enalapril. Glomerular filtration rate remained unchanged at either medication. Enalapril is an effective anti-hypertensive agent with a favourable effect on renal haemodynamics.

Antihypertensive Agents↗

Erythrocyte sodium-potassium co-transport in hypertension.

This paper reports on the measurement of sodium-potassium co-transport across red cell membranes in patients with hypertension and in normotensive volunteers. No differences were found in flux values between these two groups. Antihypertensive medication such as propranolol and enalapril (converting enzyme inhibitor) had no unequivocal effect on the measured cation transport. Individual diurnal and day-to-day variation of fluxes appear to be substantial. It is concluded that uniformity in the assay procedure may be of great importance before studying any difference in cation transport between various populations.

Adult↗

Nephroptosis and kidney function.

We have investigated the influence of renal mobility on both renal blood flow and glomerular filtration, in order to evaluate its role as a potential intermediate cause of hypertension. In 25 untreated patients we compared between recumbent and upright position the relative change in the following five parameters: effective renal plasma flow (ERPF), glomerular filtration rate (GFR), renal mobility, peripheral plasma renin activity (PRA) and blood pressure. We found a positive correlation between the degree of renal mobility and an observed decrease in ERPF. On the other hand, no relation was found between the former and an observed decrease in GFR. The PRA appeared to rise following the decrease of the ERPF. These observations suggest that renal mobility adds to the orthostatic reduction in renal blood flow.

Adult↗

Unilateral kidney blood flow measurement using the 81Rb/81mKr ratio.

A new method has been developed for the continuous quantification of kidney blood flow, utilizing the unique physical and biological properties of the radioactive tracer couple: rubidium-81/krypton-81m. After intravenous injection, 81Rb concentrates primarily in the kidneys, where it continuously generates the radioactive inert gas 81mKr. This ultrashort-lived isotope is continuously washed out from the tissue at a rate proportional to the blood flow. The radiation emitted from within the kidney is externally detected and analyzed to yield the 81Rb/81mKr ratio. 21 animal experiments have confirmed that this ratio is at any time an accurate measure of the kidney perfusion. The 81Rb/81mKr ratio method has proved to provide a non-invasive way to selectively quantify the blood flow in each kidney, to monitor perfusion changes and to image the distribution of blood flow in a functional scintigram.

Animals↗

Nephroptosis and hypertension.

The degree of renal mobility was measured in patients with and without hypertension to evaluate a suggested causal relation between nephroptosis and hypertension. In contrast to men, women often showed pronounced renal mobility and the degree of renal mobility correlated positively with the blood-pressure. Fibromuscular dysplasia of the renal artery was always accompanied by a considerable degree of renal mobility on the side involved. The results of this study indicate that in women there may be an association between abnormal renal mobility and the development of high blood-pressure.

Adolescent↗

Dose of doxorubicin determines severity of renal damage and responsiveness to ACE-inhibition in experimental nephrosis.

Nephrosis induced by doxorubicin (adriamycin) is an experimental model of glomerulosclerosis with relative stable proteinuria which is commonly used for pharmacological intervention studies. It is induced by a single or a double dose of doxorubicin, with doses that vary considerably among investigators from 2 to 7.5 mg/kg. Intervention studies with ACE-inhibitors in this model have provided conflicting results. We hypothesized that these discrepancies might be due to different properties of the doxorubicin model, related to the dose of doxorubicin used to induce proteinuria. We tested this hypothesis by inducing doxorubicin nephrosis with 1, 2 and 3 mg/kg, and evaluating the response to intervention with lisinopril. The 1-mg/kg doxorubicin dose did not induce significant proteinuria. The 2- and the 3-mg/ kg dose resulted in a proteinuria of 684+/-215 mg/24 h and 736+/-277 mg/24 h 6 weeks after induction, respectively (Mean+/-SD). Treatment with lisinopril 2 mg/kg/day reduced proteinuria to 160+/-170 mg/24 h(p<0.01) in the 2-mg/kg doxorubicin group, whereas in the 3-mg/kg doxorubicin group, proteinuria did not respond to lisinopril (529+/-264 mg/24 h). In time control rats, proteinuria remained stable. Renal damage developed in both time control groups, with a glomerulosclerosis score of 29+/-22 in the 2-mg/kg group and 84+/-41 in the 3-mg/kg doxorubicin group. Lisinopril resulted in a significantly lower glomerulosclerosis score in the 2-mg/kg doxorubicin group only (16+/-15, p<0.05), whereas the 3-mg/kg group showed no significant reduction (56+/-29, NS). In conclusion, the dose of doxorubicin used to induce nephrosis is an important determinant not only of the severity of the ensuring renal damage, but also of the response to intervention by ACE-inhibition. These findings have an impact on the interpretation of intervention studies in this model.

Angiotensin-Converting Enzyme Inhibitors↗

Potentials and limitations of the low-molecular-weight protein lysozyme as a carrier for renal drug targeting.

Selective targeting of drugs to the kidney may enable an increased renal effectiveness combined with a reduction of extrarenal toxicity. Intrarenal delivery to the proximal tubular cell can be achieved using low-molecular-weight proteins, such as lysozyme. Administration of high dosages of lysozyme, required to study the effects of such conjugates in vivo, however, is restricted since a partial escape of the renal reabsorption and the occurrence of unwanted effects on systemic blood pressure and renal function may occur. The purpose of this study was to investigate the optimal parenteral administration schedule and the maximum dose of lysozyme, providing the most optimal tubular reabsorption and at the same time a minimal effect on blood pressure and renal hemodynamics, comparing continuous infusion of lysozyme with single dose injections. Urinary lysozyme excretion increased dose-dependently, both during continuous infusion and intravenous bolus injections. However, this loss of intact lysozyme into the urine was much higher after 3 injections of in total 250 mg x kg(-1) x 6 h(-1) (51.8+/-3.7% of the dose) compared to the same dose administered by continuous infusion (11.7+/-2.4%, P < 0.001). Continuous infusion of lysozyme up to 1000 mg x kg(-1) in 6 hours had no effect on systemic blood pressure, whereas a bolus injection of lysozyme (167 mg x kg(-1)) resulted in reversible blood pressure lowering of 52.2+/-2.2% (P<0.001). A dose-dependent decline of the glomerular filtration rate was observed at dosages of lysozyme higher than 100 mg x kg(-1) x 6 h(-1), with a maximal reduction of 53.0+/-3.7% after infusion of 1000 mg x kg(-1) x 6 h(-1). Effective renal plasma flow was less affected and only lowered statistically significant at dosages of 500 (-12.6+/-3.3%, P<0.05) to 1000 mg x kg(-1) x 6 h(-1) (-17.2+/-3.9%, P<0.01). We conclude that bolus injections of lysozyme should not be used for renal targeting purposes since it results in considerable tubular loss of lysozyme in the urine as well as cardiovascular side effects. In contrast, continuous infusion of lysozyme using dosages sufficient for renal drug targeting (maximally 15 mg x kg(-1) x h(-1)) only has minimal effects on blood pressure and renal hemodynamics, with a minimal urinary lysozyme loss as well.

Animals↗