Regulation of proximal tubule transport by angiotensin II.

Angiotensin II maintains extracellular volume homeostasis, in part, by regulating proximal tubule transport. Physiological doses of angiotensin II stimulate volume and solute transport in the proximal tubule independent of changes in the glomerular filtration rate. Stimulation of bicarbonate transport primarily occurs via increasing activity of the sodium/hydrogen exchanger and the sodium/bicarbonate cotransporter. The effects of circulating angiotensin II are mediated by angiotensin II receptors on the basolateral membrane of the proximal tubule. Recently, the proximal tubule was found to synthesize and secrete angiotensin II into the lumen. The luminal membrane contains angiotensin II receptors and luminal angiotensin II levels are 100 to 200-fold higher than that found in plasma. Luminal angiotensin II receptor blockade or luminal inhibition of angiotensin II synthesis both significantly diminish proximal tubule transport, consistent with stimulation of proximal tubule transport by endogenously produced and luminally secreted angiotensin II. These data provide evidence for an autocrine/paracrine role for angiotensin II that functions independent of circulating angiotensin II.