, Volume 62, Issue 11, pp 885-892
Date: 09 Sep 2006

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

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Objective

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.

Methods

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.

Results

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 ∼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 Ca2+ channel blocker amlodipine (5 mg) on GFR and HCT-induced Na+ excretion equalled that obtained with the AT1 blocker, yet with this treatment K+ excretion rose in proportion to Na+ excretion. The β-blockers propranolol (80 mg) or bisoprolol (5 mg) reduced GFR but maintained TGF. HCT-induced Na+ excretion was significantly reduced in the presence of a β-blocker, whereas K+ excretion was not changed. The inhibition of cyclooxygenase by diclofenac (50 mg) or rofecoxib (25 mg) significantly reduced the diuretic/natriuretic effect of HCT, but K+ excretion was unchanged, and TGF was still demonstrable.

Conclusion

In conclusion, AT1 receptors, as well as the Ca2+ channels in the smooth muscle cells of the afferent arteriole, are considered prerequisites for TGF function; their blockade increases the diuretic/natriuretic efficacy of thiazide diuretics. In contrast, β-blockers and COX inhibitors do not interfere directly with TGF. These first dose effects reflect the primary response of the kidney to the drugs. They cannot, however, predict the benefits of long-term treatment.