Effects of repeated doses of enalapril on renal function in man.

Abstract

Ten healthy subjects received 10 mg oral enalapril (MK 421) daily for a period of 8 days. Renal clearances of electrolytes, urate and phosphate were monitored and factored for glomerular filtration rate, as measured by creatinine clearance, with particular emphasis on the first and eighth day of treatment. Apart from a fall of around 10% in creatinine clearance between 1‐2 h on both days 1 and 8, GFR remained unchanged throughout the study. Fractional sodium excretion increased in a biphasic manner by approximately 50% over control between 1‐2 h and 4‐8 h on day 1. Significant chloruresis (+39.0 +/‐ 12.9%) and kaluresis (+26.5 +/‐ 10.3%) occurred between 4‐8 h. Urinary pH increased between 0‐1 h (+0.29 +/‐ 0.12; P less than 0.05), and between 4‐8 h (+0.50 +/‐ 0.08; P less than 0.01). The biphasic saluretic effect was also seen between 1‐2 h and 4‐8 h on day 8. Enalapril caused significant increases in urate and phosphate excretion on day 8 of therapy. There was a biphasic increase in fractional urate excretion at 1‐2 h (+28.1 +/‐ 6.9%; P less than 0.05) and at 4‐8 h (+21.0 +/‐ 6.0% P less than 0.01). Significant phosphaturia (+36.8 +/‐ 5.2%; P less than 0.05) was also observed at 4‐8 h on day 8. Urinary drug excretion was also biphasic; over the first 2 h the predominant drug form was unchanged enalapril, whilst the peak excretion of the diacid metabolite, enalaprilat, occurred at 4‐8 h.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effect of Converting Enzyme Inhibition on the Enhanced Proximal Sodium Reabsorption Induced by Chronic Diuretic Treatment in Patients with Essential Hypertension

“…Reports on a chronic natriuretic effect of enalapril are less consistent: McNabb et al [23] reported a volume depletion still to be present after 1 week of treatment, but others saw no effect [22,24]. In the present study, we found neither an acute natriuresis nor any evidence for sodium depletion after 2 weeks.…”

“…Angiotensin-converting enzyme (ACE) inhibitors as enalapril exert some natriuretic effect in acute studies in man [20][21][22][23]. Reports on a chronic natriuretic effect of enalapril are less consistent: McNabb et al [23] reported a volume depletion still to be present after 1 week of treatment, but others saw no effect [22,24].…”

Evolution of diuretics and ACE inhibitors, their renal and antihypertensive actions‐parallels and contrasts.

“…Natriuresis occurs with captopril and enalapril in normotensive and hypertensive subjects on both normal and low sodium intakes (MacGregor et al, 1980;de Zeeuw et al, 1983;Lant et al, 1984). A concomitant rise in urinary phosphate and urate excretion (de Zeeuw et al, 1983;Leary et al, 1985;McNabb et al, 1985) suggests that ACE inhibition may also be directly inhibiting proximal tubular transport of these ions.…”

“…A concomitant rise in urinary phosphate and urate excretion (de Zeeuw et al, 1983;Leary et al, 1985;McNabb et al, 1985) suggests that ACE inhibition may also be directly inhibiting proximal tubular transport of these ions.…”

The effects of cilazapril alone and in combination with frusemide in healthy subjects.

“…The effect on the glomerular filtration rate is variable and depends on the experimental conditions (Mimran et al, 1979;Hollenberg et al, 1981;McNabb et al, 1986;Navis et al, 1986). Captopril and enalapril cause acute natriuresis (Brunner et al, 1981;Hollenberg et al, 1981;McNabb et al, 1986;Navis et al, 1986) which may be accompanied by potassium retention (Atlas et al, 1979;Navis et al, 1986) or in the case of enalapril by kaliuresis (McNabb et al, 1985(McNabb et al, , 1986. Both drugs have been reported to increase prostaglandin levels (Swartz et al, 1980;Oparil et al, 1983) but there are no data for cilazapril.…”