Skip to main content
SpringerLink
Log in

Natriuretic Effect and Changes in Renal Haemodynamics Induced by Enalapril in Essential Hypertension

  • Section 2: Enalapril: Pharmacodynamic Findings and Therapeutic Efficacy in Hypertension and Heart Failure
  • Published:
Drugs Aims and scope Submit manuscript

Summary

The purpose of this study was to evaluate the natriuretic effect and renal haemodynamic changes induced by enalapril in patients with essential hypertension. In a group of 11 patients with mild to moderate hypertension with normal renal function, and on a controlled sodium intake (80 mmol/day), a decrease in systolic and diastolic blood pressure was observed (p <0.001) after 16 weeks of enalapril treatment (20 mg/day), without a change in heart rate. An increase in plasma renin activity (p <0.05) without changes in serum aldosterone, and a decrease in exchangeable sodium (p <0.001) were present at the end of the treatment period.

In 10 hypertensive patients also taking a dietary sodium of 80 mmol/day, the renal haemodynamics, humoral changes, and urinary sodium excretion were measured during 4 days of enalapril treatment (20 mg/day). There was an increase in urinary sodium excretion on the 3rd and 4th days of treatment (p < 0.01). The effective renal plasma flow and fractional sodium excretion increased 72 hours after the beginning of treatment (p < 0.01); the glomerular filtration rate did not change, and filtration fraction decreased at 72 hours. Mean blood pressure fell 2 hours after the first dose (p <0.01), and the maximum drop in intrarenal vascular resistance occurred after 72 hours of treatment (p <0.01). Plasma renin activity increased (p < 0.05) and serum aldosterone decreased (p <0.01) 2 hours after the first dose. Thereafter, serum aldosterone increased progressively until it reached values similar to those with placebo at 48 and 72 hours of treatment. Urinary kallikrein fell during the 2nd and 3rd day of treatment (p <0.01). It was concluded that the decrease in exchangeable sodium was due to a natriuretic effect of enalapril. This effect presumably results from renal haemodynamic changes due to the reduction of angiotensin II. Other mechanisms, such as the reduction of aldosterone and accumulation of kinins, could be contributory factors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Anderson, G.H.; Springer, J.; Tivnan, E.; Kearney, H. and Streeten, D.H.P.: Hypotensive mechanism of captopril. Clinical Research 28: 328A(1980).

    Google Scholar 

  • Atkinson, A.B.; Brown, J.J.; Fraser, R.; Leckie, B.; Lever, A.F.; Morton, J.J. and Robertson, J.I.S.: Captopril, angiotensin II and sodium in blood pressure regulation. Lancet 1: 1140 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Atkinson, A.B. and Robertson, J.I.S.: Captopril in the treatment of clinical hypertension and cardiac failure. Lancet 2: 836–839 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Atkinson, A.B.; Morton, J.J.; Brown, J.J.; Davies, D.L.; Kelly, P.; Leckie, B.; Lever, A.F. and Robertson, J.I.S.: Captopril in clinical hypertension. Changes in components of the renin-angiotensin system and in body composition in relation to fall in blood pressure with a note on measurement of angiotensin II during converting enzyme inhibition. British Heart Journal 44: 290–296 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Atlas, S.A.; Case, D.B.; Sealey, J.E.; Laragh, J.H. and McKinstry, D.N.: Interruption of the renin-angiotensin system in hypertensive patients by captopril induces sustained reduction in aldosterone secretion, potassium retention and natriuresis. Hypertension 1: 274–280 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Biollaz, J.; Brunner, H.R.; Gavras, I.; Waeber, B. and Gavras, H.: Antihypertensive therapy with MK 421: Angiotensin II-renin relationships to evaluate efficacy of converting enzyme blockade. Journal of Cardiovascular Pharmacology 4: 966–972 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Brown, J.J.; Casals-Stenzel, J.; Cumming, A.M.M.; Davies, D.L.; Fraser, R.; Lever, A.F.; Morton, J.J.; Semple, P.F.; Tree, M. and Robertson, J.I.S.: Angiotensin II, aldosterone and arterial pressure: A quantitative approach. Hypertension 1: 159–179 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Brunner, D.B.; Desponds, G.; Biollaz, J.; Keller, I.; Ferber, F.; Gavras, H.; Brunner, H.R. and Schelling, J.L.: Effect of a new angiotensin converting enzyme inhibitor MK-421 and its lysine analogue on the components of the renin system in healthy subjects. Journal of Cardiovascular Pharmacology 11: 461–467 (1981).

    CAS  Google Scholar 

  • Brunner, H.R.; Gavras, H.; Waeber, B.; Korshow, G.R.; Turini, G.A.; Vukovich, R.A.; McKinstry, D.N. and Gavras, I.: Oral angiotensin converting inhibitor in long-term treatment of hypertensive patients. Annals of Internal Medicine 90: 19–23 (1979).

    PubMed  CAS  Google Scholar 

  • Brunner, H.R.; Gavras, H.; Waeber, B.; Textor, S.G.; Turini, G.A. and Wanters, J.P.: Clinical use of an orally acting converting enzyme inhibitor: Captopril. Hypertension 2: 558–564 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Brunner, H.R.; Waeber, B.; Nussberg, J.; Schaller, M.D. and Gomez, H.J.: Long-term clinical experience with enalapril in essential hypertension. Journal of Hypertension 1 (Suppl. 1): 103–107(1983).

    Article  PubMed  CAS  Google Scholar 

  • Case, D.B.; Atlas, S.A.; Laragh, J.H.; Sealey, J.E.; Sullivan, P.A. and McKinstry, D.M.: Clinical experience with blockade of the renin-angiotensin-aldosterone system by an oral converting enzyme inhibitor (S.Q. 14224, captopril) in hypertensive patients. Progress in Cardiovascular Diseases 21: 195–206 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Claeson, G.; Friberger, E.; Knos, O. and Eriksson, E.: Methods for determinations of prekallikrein in plasma, glandular kallikrein and urokinase. Haemostasis 7: 76–78 (1978).

    PubMed  CAS  Google Scholar 

  • Cody, R.J.; Laragh, J.H.; Atlas, S.A. and Case, D.B.: Converting enzyme inhibition to identify and treat renin-mediated or sodium volume related forms of increased peripheral resistance in hypertension and in congestive heart failure. Journal of Hypertension 1 (Suppl. 1): 77–84(1983).

    PubMed  CAS  Google Scholar 

  • Davies, D.L.; Beevers, D.G.; Brown, J.J.; Cumming, A.M.M.; Fraser, R.; Lever, A.F.; Mason, P.A.; Morton, J.J.; Robertson, J.I.S.; Titterington, M. and Tree, M.: Aldosterone and its stimuli in normal and hypertensive man: Are essential hypertension and primary hyperaldosteronism without tumour the same condition? Journal of Endocrinology 81: 79P-91P (1979

  • de Leeuw, P.W.; Hoogma, R.P.L.M.; van Soest, G.A.W.; van Es, P.N. and Birkenhäger, W.H.: Physiological effects of short-term treatment with enalapril in hypertensive patients. Journal of Hypertension 1 (Suppl. 1): 87–91 (1983).

    PubMed  Google Scholar 

  • de Zeeuw, D.; Navis, G.J.; Donker, A.J.M. and deJong, P.E.: The angiotensin converting enzyme inhibitor enalapril and its effects on renal function. Journal of Hypertension 1 (Suppl. 1): 93–97 (1983).

    PubMed  Google Scholar 

  • Edwards, R.M.: Response of isolated renal microvessels to inraluminal pressure, norepinephrine and angiotensin II. Abstracts of the 15th Annual Meeting of the American Society of Nephrology, Chicago p. 150 (1982).

  • Fitzpatrick, D.; Nicholls, M.G.; Ikram, H. and Espiner, E.A.: Acute haemodynamic, hormonal and electrolyte effects and short-term clinical response to enalapril in heart failure. Jourrraf of Hypertension 1 (Suppl. 1): 147–153 (1983).

    CAS  Google Scholar 

  • Fraser, R.; Brown, J.J.; Lever, A.F.; Mason, P.A. and Robertson, J.I.S.: Control of aldosterone secretion. Clinical Science 56: 389–392 (1979).

    PubMed  CAS  Google Scholar 

  • Gavras, H.; Gavras, I.; Textor, S.; Volices, L.; Brunner, H.R. and Rolieska, E.J.: Effect of angiotensin converting enzyme inhibition on blood pressure, plasma renin activity and plasma aldosterone in essential hypertension. Journal of Clinical Endocrinology and Metabolism 46: 220–226 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Gavras, H.; Biollaz, J.; Waeber, B.; Brunner, H.R.; Gavras, I. and Davies, R.D.: Antihypertensive effect of the new oral angiotensin converting enzyme inhibitor ‘MK-421’. Lancet 2: 543–547 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Giménez, M.; Grunfeld, B.; Simsolo, R.; Mendilharzu, F.; Barontini, M. and Becú, L.: Kalicreína urinaria en distintas formas de hipertensión en pediatria. Medicina (Buenos Aires) 42: 736–737 (1982).

    Google Scholar 

  • Hall, J.E.; Guyton, A.C.; Trippodo, N.C.; Lohmeier, T.E.; McCaa, R.E. and Cowley, A.W.: Intrarenal control of electrolyte excretion by angiotensin II. American Journal of Physiology 233: F538–F544 (1977).

    Google Scholar 

  • Hall, J.E.; Coleman, T.G.; Guyton, A.C.; Balfe, J.W. and Salgado, H.C.: Intrarenal role of angiotensin II and (des-Asp1) angiotensin II. American Journal of Physiology 236: F252–F259 (1979).

    PubMed  CAS  Google Scholar 

  • Hodsman, G.P.; Brown, J.J.; Cumming, A.M.M.; Davies, D.L.; East, B.W.; Lever, A.F.; Morton, J.J.; Murray, G.D. and Robertson, J.I.S.: Enalapril (MK-421) in the treatment of hypertension with renal artery stenosis. Journal of Hypertension 1 (Suppl. 1): 109–117 (1983).

    PubMed  CAS  Google Scholar 

  • Hollenberg, N.K.; Swartz, J.L.; Passan, D.R. and Williams, G.H.: Increased glomerular filtration rate after converting enzyme inhibition. New England Journal of Medicine 301: 9–12 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Hollenberg, N.K.; Meggs, L.G.; Williams, G.H.; Katz, J.; Garnic, J.D. and Harrington, D.P.: Sodium intake and renal responses to captopril in normal man and in essential hypertension. Kidney International 20: 240–245 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Hollenberg, N.K. and Williams, G.H.: Volume control and altered renal and adrenal responsiveness to angiotensin in essential hypertension: Implications for treatment with converting enzyme inhibition. Journal of Hypertension 1 (Suppl. 1): 119–128 (1983).

    PubMed  CAS  Google Scholar 

  • Hricik, D.E.; Browning, P.J.; Kopeleman, R.; Goormo, W.E.; Madias, N.E. and Dzau, V.J.: Captopril induced functional renal insufficiency in patients with bilateral renal artery stenosis or renal artery stenosis in a solitary kidney. New England Journal of Medicine 308: 373–376 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Johnston, C.I.; McGrath, B.P.; Millar, J.A. and Matthews, P.G.: Long-term effects of captopril (SQ 14225) on blood pressure and hormone levels in essential hypertension. Lancet 2: 493–495 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Johnston, C.I.; McGrath, B.P.; Matthews, P.G. and Jackson, B.: Treatment of hypertension with angiotensin converting enzyme inhibitors. Clinical and Experimental Pharmacology and Physiology 7 (Suppl.): 135–144 (1982).

    CAS  Google Scholar 

  • Karlberg, B.E.; Ohman, K.P.; Nilsson, O.R. and Wettre, S.: Captopril lowers urinary kallikrein in hypertensive patients. Lancet 1: 150–151 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Kjekshus, J.K.; Syland, E.; Dickstein, K.; Abrahamsen, A.M. and Gundersen, T.: Sustained haemodynamic effects of enalapril in left ventricular failure. Journal of Hypertension 1 (Suppl. 1): 143–145(1983).

    PubMed  CAS  Google Scholar 

  • Levens, N.R.; Peach, M.J. and Casey, R.M.: Role of the intrarenal renin-angiotensin system in the control of renal function. Circulation Research 48: 157–167 (1981).

    Article  PubMed  CAS  Google Scholar 

  • MacGregor, G.A.; Markandu, N.D.; Bayliss, J.; Roulston, J.E.; Squires, M. and Morton, J.J.: Non sulphydryl containing angiotensin converting enzyme inhibitor (MK-421); evidence for a role of renin system in normotensive subjects. British Medical Journal 23: 401–403 (1981).

    Article  Google Scholar 

  • McCaa, R.E.; Hall, J.E. and McCaa, C.S.: The effects of angiotensin I converting enzyme inhibitors on arterial blood pressure and urinary sodium excretion. Role of renal renin-angiotensin and kallikrein-kinin systems. Circulation Research 43 (Suppl. 1): 32–39(1978).

    CAS  Google Scholar 

  • Meggs, L.G. and Hollenberg, N.K.: Converting enzyme inhibition and the kidney. Hypertension 2: 551–557 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Morganti, A.; Pickering, T.G.; Lopez Ovejero, J.A. and Laragh, J.H.: Endocrine and cardiovascular influences of converting enzyme inhibition with SQ 14225 in hypertensive patients in the supine position and during head-up tilt before and after sodium depletion. Journal of Clinical Endocrinology and Metabolism 50: 748–754(1980).

    Article  PubMed  CAS  Google Scholar 

  • Ondetti, M.A.; Rubin, B. and Cushman, D.W.: Design of specific inhibitors of angiotensin converting enzyme. Science 196: 441–444 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Osgood, R.W.; Reineck, H.J. and Stein, J.H.: Effect of volume expansion on sodium transport in the proximal tubule of juxtamedullary nephrons. Clinical Research 25: 444A-450A (1977).

    Google Scholar 

  • Romankiewicz, J.A.; Brogden, R.N.; Heel, R.C.; Speight, T.M. and Avery, G.S.: Captopril: An update review of its pharmacological properties and therapeutic efficacy in congestive heart failure. Drugs 25: 6–40 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Sánchez, R.A.; Cavarra, O.; Brea, S.A.; Marcó, E.J.; Ravera, M. and Moledo, L.I.: Actividad renínica plasmática en la hipertensión esencial. Medicina (Buenos Aires) 39: 171–177 (1979).

    Google Scholar 

  • Sánchez, R.A.; Marco, E.J.; Brea, S.A.; Bourges, M.M.; Gilbert, B.H. and Moledo, L.I.: Sodio total intercambiable en la hipertensión esencial e hipertensión con insuficiencia renal crónica. Medicina (Buenos Aires) 41: 153–156 (1981).

    Google Scholar 

  • Schnurr, E.; Lahme, W. and Kuppers, H.: Measurement of renal clearance of inulin and PAH in the steady state without urine collection. Clinical Nephrology 13: 26–29 (1980).

    PubMed  CAS  Google Scholar 

  • Shoback, D.M.; Williams, G.H.; Swartz, S.L.; Davies, R.O. and Hollenberg, N.K.: Time course and effect of sodium intake on vascular and hormonal responses to enalapril (MK-421) in normal subjects. Journal of Cardiovascular Pharmacology 5: 1010–1018 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Simon, G.; Morioka, S.; Snyder, D.K. and Cohn, J.N.: Increased renal plasma flow during long-term treatment of essential hypertension with MK-421. (Abstract 660.) Circulation 66: 166 (1982).

    Article  Google Scholar 

  • Smith, H.W.; Goldring, W. and Chasis, H.: The measurement of the tubular excretory mass, effective blood flow and filtration rate in the normal human kidney. Journal of Clinical Investigation 17: 263–278 (1938).

    Article  PubMed  CAS  Google Scholar 

  • Staessen, J.; Lijnen, P.; Fagard, R.; Verschueren, L.J. and Amery, A.: Rise of plasma aldosterone during long-term captopril treatment. New England Journal of Medicine 304: 1110 (1981).

    PubMed  CAS  Google Scholar 

  • Stein, J.H.; Osgood, R.W. and Kunau, R.T.: Direct measurement of papillary collecting duct sodium transport in the rat: Evidence for heterogeneity of nephron function during Ringer’s loading. Journal of Clinical Investigation 58: 767–773 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Swartz, S.L.; Williams, G.H.; Hollenberg, N.F.; Grantz, F.R.; Moore, T.J.; Levine, L.; Sadahra, A.A. and Dluhy, R.G.: Endocrine profile in the long-term phase of converting enzyme inhibition. Clin. Pharmacol, and Ther. 28: 499–504 (1980).

    Article  CAS  Google Scholar 

  • Sweet, C.S.; Gaul, S.L.; Reitz, P.M.; Blaine, E.H. and Ribeiro, L.T.: Mechanism of action of enalapril in experimental hypertension and acute left ventricular failure. Journal of Hypertension 1 (Suppl. 1): 53–63 (1983).

    PubMed  CAS  Google Scholar 

  • Taylor, T.; Moore, T.J.; Hollenberg,N.K. and Williams, G.H.: Converting-enzyme inhibition corrects the altered adrenal response to angiotensin II in essential hypertension. Hypertension 6: 92–99 (1984).

    Article  PubMed  CAS  Google Scholar 

  • Underwood, R.H. and Williams, G.H.: The simultaneous measurement of aldosterone cortisol and corticosterone in human peripheral plasma by displacement analysis. Journal of Laboratory and Clinical Medicine 79: 848–862 (1972).

    PubMed  CAS  Google Scholar 

  • Waeber, B.; Brunner, H.R.; Brunner, D.B.; Curtet, A.; Turini, G.A. and Gavras, H.: Discrepancy between antihypertensive effect and angiotensin converting enzyme inhibition by captopril. Hypertension 2: 236–242 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Wenting, G.J.; Man Int’Veld, A.J.; Woitteuz, A.J.; Boomsma, F.; Laird-Meeter, K.; Simoons, M.L.; Hugenholtz, P.G. and Schalekamp, M.A.D.: Effects of captopril in acute and chronic heart failure. Correlations with plasma levels of noradrenaline, renin and aldosterone. British Heart Journal 49: 65–73 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Zimmerman, B.G. and Wong, P.C.: Alterations in renal function produced by angiotensin converting enzyme inhibitors; in Horovitz (Ed.) Angiotensin Converting Enzyme Inhibitors, pp. 239–253 (Urban and Schwarzenberg, Baltimore 1981).

Download references

Author information

Authors and Affiliations

  1. Academia Nacional de Medicina and Hospital de Ninos Ricardo Gutierrez, Hospital Instituto de Cardiologia, Coronel Diaz 2423, 1425, Buenos, Aires, Argentina

    R. A. Sánchez, E. Marcó, H. B. Gilbert, P. Raffaele, M. Brito, M. Giménez &  L. I. Moledo

Authors
  1. R. A. Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Marcó
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. B. Gilbert
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Raffaele
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Brito
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Giménez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L. I. Moledo
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sánchez, R.A., Marcó, E., Gilbert, H.B. et al. Natriuretic Effect and Changes in Renal Haemodynamics Induced by Enalapril in Essential Hypertension. Drugs 30 (Suppl 1), 49–58 (1985). https://doi.org/10.2165/00003495-198500301-00008

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-198500301-00008

Keywords

Search

Navigation