Renal effects of angiotensin II receptor blockade in normotensive subjects.
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.
Burnier
M
M
Division of Hypertension, CHUV, Lausanne, Switzerland.
Roch-Ramel
F
F
Brunner
H R
HR
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000502:physiology*; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin