Copyright © 1992 by the European Society of Cardiology.
© 1992 The European Society of Cardiology
Comparative mechanisms of action of diuretic drugs in hypertension
Departments of Pharmacotherapy and Cardiology, University of Amsterdam The Netherlands
Correspondence: Professor P. A. van Zwieten, Departments of Pharmacotherapy and Cardiology. Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
This review concerns the modes of action of thiazides, loop- and potassium-sparing diuretics, with particular emphasis on their antihypertensive activity. Thiazide diuretics inhibit an enzyme in the basolateral cell membrane in the distal tubule, thus bringing about an impaired absorption and enhanced excretion of both Na+ and Cl– ions. The loss of Na+ ions is countered by the exchange from Na + against K+, hence causing a loss of K+ ions. The renal excretion of Ca++ ions is impaired, that of Mg++ ions enhanced.
Loop diuretics inhibit a carrier mechanism that enhances the inward transport into the tubular cells of Na+, K+ and Cl– ions as well as water. This process, which occurs in the thick ascending limb of Henle's loop, enhances the urinary excretions of these ions together with water and Ca++ and Mg++ ions.
Potassium-sparing diuretics comprise two different categories. Triamterene and amiloride inhibit a local transport mechanism in the distal tubular cells which allows the influx of Na+ and its exchange against K+ or H+ ions. Concomitantly, the excretion of Na+, but not that of K+, ions is enhanced. Aldosterone antagonists inhibit the renal effects of aldosterone at the receptor level and impair the reabsorption of Na+ ions and water and their exchange against K+ ions.
Despite detailed knowledge of the renal mode of action of the diuretics, the mechanism whereby they exert their antihypertensive activity is still uncertain. The initial reduction in plasma volume is accompanied by reduction in cardiac output and increased systemic vascular resistance. Continued treatment leads to a return to normal in cardiac output and a reduction in systemic vascular resistance. The mechanism of action of the different diuretic groups on the haemodynamic variables controlling blood pressure awaits clarification.
Key Words: Hypertension • diuretics • haemodynamic mechanisms
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