Renal effects of angiotensin II receptor blockade in normotensive subjects

Abstract

Several new non-peptide, orally active, angiotensin II receptor antagonists have recently been developed which enable to block the renin-angiotensin system at the AT1 receptor site. In contrast to angiotensin converting enzyme (ACE) inhibitors, these antagonists do not interfere with the metabolism of kinins. The effect of these agents on renal function may thus potentially differ from those of ACE inhibitors. Therefore, the renal pharmacology of various angiotensin II receptor antagonists has been examined in normotensive subjects. In normotensive subjects, losartan and irbesartan have been shown to have no effect on glomerular filtration rate and to induce either no change or a modest increase in renal blood flow. These results were confirmed thereafter in hypertensive patients where losartan produced a renal vasodilation with no change in glomerular filtration. In healthy subjects, both losartan and irbesartan induce an acute increase in urinary sodium excretion. The natriuretic response to losartan is proportionally more important during salt-depletion. In contrast to other angiotensin II receptor antagonists, losartan has a unique property to increase uric acid excretion. In this paper we show that this property is due to the potent inhibitory effect of the parent compound of losartan on the urate/anion transport in the human renal proximal tubule.

High-Normal Serum Uric Acid Is Associated with Impaired Glomerular Filtration Rate in Nonproteinuric Patients with Type 1 Diabetes

“…Thiazide diuretics reportedly increase whereas losartan and ACEi lower uric acid levels (41)(42)(43). In our study, uric acid levels were significantly higher among patients who reported use of thiazide diuretics but use did not confound the relationship between uric acid and cC-GFR.…”

Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism

“…However, losartan's effect could be mediated in part by its known uricosuric action (20), because uric acid levels tended to be lower in the losartan-treated rats. The ability of losartan to lower uric acid is unique to losartan and is not observed in other AT 1 receptor antagonists (3). Further studies will be required to determine whether losartan provides any superior effect over other means for blocking the renin-angiotensin system in hyperuricemic rats.…”

“…3A), and both prevented the arteriolopathy (Table 3). Interestingly, uric acid levels tended to be lower in the losartan group compared with untreated controls (P ϭ 0.054, Table 3), which likely relates to the fact that losartan has some uricosuric activity (3,20).…”

Impact of the Angiotensin II Receptor Antagonist, Losartan, on Myocardial Fibrosis in Patients with End-Stage Renal Disease: Assessment by Ultrasonic Integrated Backscatter and Biochemical Markers

“…Since regression of the myocardial fibrosis was observed only in the losartan-treated group, the anti-fibrotic effect of improving anemia might not be significant over 6 months. A feature of losartan that differentiates it from other AT1-R antagonists is its lowering of serum UA (42), but this effect is due to the ability of the losartan molecule (not its active metabolite) to interfere with urate reabsorption in the renal proximal tubules (43). Thus its effects are closely related to renal function.…”