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Should the use of short acting angiotensin-converting enzyme inhibitors be abandoned?

Institute of Hypertension and Kidney Diseases, Rabin Medical Center (Beilinson Campus) Petah Tikva and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

Geoffrey Boner

Institute of Hypertension and Kidney Diseases, Rabin Medical Center (Beilinson Campus) Petah Tikva and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel, gboner@ clalit.org.il

David J van Dijk

Institute of Hypertension and Kidney Diseases, Rabin Medical Center (Beilinson Campus) Petah Tikva and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

Background Angiotensin-converting enzyme inhibitors (ACE-I) have different modes of action and different durations of inhibition. The effects of ACE-I on the various components of the renin-angiotensin system (RAS) at trough hours were studied in patients with diabetes mellitus receiving long-term ACE-I treatment.

Methods Out of 86 Type 1 and 2 diabetic patients, 49 were untreated, 25 received captopril and 12 received enalapril as chronic treatment. Blood for the determination of plasma renin activity (PRA), serum ACE activity and plasma angiotensin II (Ang II) was drawn in the morning (0700—0900 hours) after an overnight fast, about 12 hours after the last dose. PRA and Ang II were measured by RIA and serum ACE activity was assayed by a radiometric assay using ³H-hippuryl-glycyl-glycine as a substrate.

Results Mean age was significantly greater in the enalapril-treated patients. Systolic and diastolic blood pressures were not different between the captopril-treated and untreated groups. Serum ACE activity in the captopril-treated diabetic patients was 101.5±42.5 nmol/mL/min, values obtained in untreated diabetic patients (101.4±25.2 nmol/mL/min). In contrast, ACE activity in the enalapril-treated patients was significantly reduced (5.5±7.5 nmol/mL/min) compared with untreated and captopril-treated patients (p<0.00001). PRA values in the ACE-I treated patients were significantly increased. Plasma Ang II levels were significantly increased in the captopril-treated vs. untreated patients (65.1±50.2 vs. 36.2±31.7 pg/mL, p=0.006), whereas the values in the enalapril-treated patient were slightly, but not significantly, reduced (23.8±21.4 pg/mL).

Conclusion Trough serum ACE activity is not suppressed in diabetic patients receiving captopril, compared with those receiving enalapril and we thus question the use of short acting ACE-I in these patients.

Key Words: ACE • ACE inhibitors • angiotensin • diabetes mellitus

References

• Urata H., Healy B., Stewart RW, Bumpus FM, Hussain A. Angiotensin II-forming pathways in normal and failing human hearts. Circ Res 1990; 66: 883-90.[Abstract/Free Full Text]
• Christlieb AR Renin-angiotensin system in diabetes mellitus. Diabetes 1976; 2(Suppl 2): 820-5.
• van Dijk DJ, Erman A., Chen-Gal B., Sulkes J., Boner G. Increased serum converting enzyme activity in type I insulin-dependent diabetes mellitus: its relation to metabolic control and diabetic complications. Eur J Clin Invest 1994; 24: 463-7.[Web of Science][Medline] [Order article via Infotrieve]
• Schernthaner G., Schwarzer CH, Kuzmits R., Muller MM, Klemen U., Frelyler H. Increased angiotensin converting enzyme in diabetes mellitus: analysis of diabetes type, state of the metabolic control and occurrence of diabetic vascular disease. J Clin Pathol 1984; 37: 307-12.[Abstract/Free Full Text]
• Parving HH,AndersenAR, Smidt UM, Hommel E., Mathiesen E., Svendsen PA Effects of antihypertensive treatment on kidney function in diabetic nephropathy. Br Med J1987; 294: 1443-7.[Abstract/Free Full Text]
• Jerums G. Differences in renal outcomes with ACE inhibitors in type 1 and 2 diabetic patients: possible explanations. Miner Electrolyte Metab 1988; 24: 423-37.[CrossRef]
• Meiracker AH, Man AJ, Admiral PJJ et al. Partial escape of angiotensin converting enzyme (ACE) inhibition during prolonged ACE inhibitor treatment: does it exist and does it affect the hypertensive response? J Hyperten 1992; 10: 803-12.[Web of Science][Medline] [Order article via Infotrieve]
• Borghi C., Boschi S., Ambrosioni E., Melandri G., Branzi A., Magnani B. Evidence of a partial escape of renin-angiotensin-aldosterone blockade in patients with acute myocardial infraction treated with ACE inhibitors. J Clin Pharmacol 1993; 33: 40-5.[Abstract]
• Erman A.,van Dijk DJ, Chen-Gal B., Giler S., Rosenfeld JB, Boner G. Angiotensin converting enzyme activity in the serum, lung, and kidney of diabetic rats. Eur J Clin Invest 1993; 23: 615-20.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Roulston JE, MacGregor GA The measurement of angiotensin converting enzyme in subjects receiving captopril. N Engl J Med 1980; 303: 397.[Web of Science][Medline] [Order article via Infotrieve]
• Kamoun PP, Bardet JI, Di Giulio S., Grunfeld JP Measurement of angiotensin converting enzyme in captopril-treated patients. Clin Chem Acta 1982; 118:333-6.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Mooser V., Nussberger J., Jullirat L. et al. Reactive hyperreninemia is the major determinant of plasma angiotensin II during ACE inhibition. J Cardiovasc Pharmacol 1990; 15: 276-82.[Web of Science][Medline] [Order article via Infotrieve]
• Nussberger J.,Waeber B., Brunner HR Plasma angiotensin II and the hypertensive action of angiotensin converting converting enzyme inhibition. Am JHyperten 1993; 2: 286-93.
• Nussberger J., Menard J., Mooser V. et al. Determinants of angiotensin II generation during converting enzyme inhibition. Hypertension 1990; 16: 564-72.[Abstract/Free Full Text]
• Wilkes BM Evidence for vasodepressor effect of angiotensin converting enzyme inhibitor, MK421 (enalapril), independent of blockade of angiotensin II formation. J Cardiovasc Pharmacol 1984; 6: 1036-42.[Web of Science][Medline] [Order article via Infotrieve]
• Erman A., Winkler J., Chen-Gal B. et al. Inhibition of angiotensin converting enzyme by ramipril in serum and tissue of man. J Hyperten 1991; 9:1057-62.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Murakami M., Matsuda H., Kubota E. et al. Role of angiotensin II generated by angiotensin converting enzmeindependent pathways in the canine kidney. Kidney International 1997; 52(Suppl 63):S132-S135.
• Derkx FHM,Tan-Tjiong L., Wenting GJ et al. Asynchronous changes in prorenin and renin secretion after captopril in patients with renal artery stenosis. Hypertension 1983; 5: 244-56.[Abstract/Free Full Text]
• Derkx FHM, Wenting GJ, Man in `t Veld AJ, Verhopeven RP, Schalekamp Madh. Control of enzymatically inactive renin in man under various pathological conditions. Clin Sci Mol Med 1978; 54: 529-38.[Medline] [Order article via Infotrieve]
• Hansson L., Lindholm LR, Niskanen L. et al. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the captopril prevention project (CAPPP) randomized trial. Lancet 1999; 353:611-6.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Mathiesen ER, Hansen HP, Smidt UM, Parving HH Randomized controlled trial of long term efficacy of captopril on preservation of kidney function in normotensive patients with insulin dependent diabetes and microalbuminuria. BMJ 1999; 319: 24-5.[Free Full Text]
• Griffin SA, Brown WC, MacPherson F. et al. Angiotensin II causes vascular hypertrophy in part by non-pressor mechanism. Hypertension 1991; 17: 626-35.[Abstract/Free Full Text]
• Kagami S., Border WA, Miller DE, Noble NA Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-beta in rat glomerular mesangial cells. J Clin Invest 1994; 92: 2431-7.
• Lewis EJ, Hunsicker LG, Bain RP, Rohde RD, for the Collaborative Study Group. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Eng J Med 1993; 329: 1456-62.[Abstract/Free Full Text]

Journal of Renin-Angiotensin-Aldosterone System, Vol. 1, No. 4, 365-368 (2000)
DOI: 10.3317/jraas.2000.068


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Erman, A. Articles by van Dijk, D. J Search for Related Content PubMed PubMed Citation Articles by Erman, A. Articles by van Dijk, D. J Social Bookmarking                         What's this?