Renal effects of angiotensin II receptor antagonists.
Among the many roles that angiotensin II plays in the kidney, one of the most important is the direct and indirect regulation of sodium excretion. Angiotensin II is produced within the kidney, where concentrations appear to be far in excess of those detected in plasma. High levels of angiotensin II subtype 1 receptors have been detected on the luminal side of the tubular cells in the proximal convoluted tubule, and these have been implicated in the regulation of sodium excretion. This portion of the nephron is responsible for the reabsorption of 65% of filtered sodium. It is, therefore, reasonable to assume that blockade of these receptors, using non-peptide angiotensin II receptor antagonists, will bring about an increase in renal excretion of sodium. There is, however, the possibility that, if the effect is small, downstream sites will have the capacity to reabsorb the increased sodium delivered to the distal nephron. Studies in hypertensive animal models have established that angiotensin II subtype 1 receptor antagonists stimulate natriuresis. However, the studies that have been performed to date in humans are deficient in that they have been conducted in normotensive subjects. Also, subjects have only been followed up for 6 or 8 h and thus these studies did not examine whether the observed short-term natriuresis was followed by an enhanced reabsorption of sodium. Another study, designed to overcome the deficiencies of previous studies, has investigated the natriuretic effect of telmisartan in hypertensive patients.
Burgess
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Faculty of Medicine, University of Calgary, Alberta, Canada.
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D009318:Natriuresis / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D000804:Angiotensin II