Concentrations and actions of intraluminal angiotensin II

Although the presence of angiotensin II (AngII) receptors on the luminal membranes of proximal tubule cells has been recognized for many years, recent immunohistochemical studies using polyclonal and monoclonal antibodies to the AngII type 1 (AT1) receptor have demonstrated an abundance of the AT1 receptor not only on the luminal surface of proximal tubule cells but also on the luminal surfaces of distal nephron segments. An important role for these receptors in the regulation of tubular transport mechanisms was indicated by the recent findings of remarkably high proximal intratubular concentrations of AngII (in the range of 10(-9) to 10(-8) M). The high intratubular concentrations of AngII, as well as angiotensin I and angiotensinogen, are much greater than can be explained on the basis of delivery via glomerular filtration. When coupled with the findings demonstrating the presence of angiotensinogen and angiotensinogen mRNA in proximal tubule cells, the data indicate that AngII or precursors of AngII are secreted directly into the proximal tubule lumen by the epithelial cells. Although the mechanisms responsible for the regulation of intratubular AngII concentrations remain to be determined, micropuncture studies have provided direct evidence that activation of intraluminal AT1 receptors by AngII exerts a substantial stimulatory influence on sodium and bicarbonate transport by both proximal and distal tubules. Collectively, these data provide support for the hypothesis that activation of luminal AT1 receptors by AngII present in the tubular fluid contributes importantly to regulation of the tubular reabsorption rate.