The influence of cardiovascular and antiinflammatory drugs on thiazide-induced hemodynamic and saluretic effects

European Journal of Clinical Pharmacology
Heinrich KnaufE Mutschler


Thiazide diuretics are known to induce a transient fall of the glomerular filtration rate (GFR), which, in turn, reduces tubular Na(+) load. This tubuloglomerular feedback (TGF) curtails the natriuretic effect of this class of diuretics. Cardiovascular and antiinflammatory therapeutics may interfere with TGF and thereby influence the effect of thiazides once co-administration is clinically indicated. The effects on GFR and saluresis of hydrochlorothiazide (HCT; 25 mg) monotherapy were measured in healthy volunteers and compared to those obtained during co-administration of the thiazide and a second therapeutic. In the presence of the ACE inhibitor enalapril (10 mg), the transient fall in the GFR induced by HCT was almost abolished, and Na(+) excretion increased by approximately 30 % as compared to HCT monotherapy. K(+) excretion, however, remained unchanged. Similar results were obtained with the AT II type 1 receptor antagonist candesartan (8 mg): GFR remained stable, Na(+) excretion rose by 35 % and K(+) excretion was not changed. The effect of the Ca(2+) channel blocker amlodipine (5 mg) on GFR and HCT-induced Na(+) excretion equalled that obtained with the AT(1) blocker, yet with this treatment K(+) excretion rose in propor...Continue Reading


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