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REGULATION OF PROXIMAL TUBULE FUNCTION BY ANGIOTENSIN
Author(s) -
Harris Peter J.
Publication year - 1992
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1992.tb00441.x
Subject(s) - proximal tubule , function (biology) , angiotensin ii , tubule , renin–angiotensin system , endocrinology , medicine , chemistry , microbiology and biotechnology , biology , kidney , receptor , blood pressure
SUMMARY 1. Independent of its effects on renal haemodynamics and glomerular filtration, angiotensin II (All) has direct actions on the proximal tubule involving transepithelial Na + , H + , HCO 3 ‐ , and water reabsorption, ammoniagenesis, gluconeogenesis and renal growth. 2. The effects of AH on water and electrolyte transport are biphasic and dose‐dependent, such that low concentrations (10 ‐12 –10 ‐9 mol/L) stimulate reabsorption whereas high concentrations (10 ‐7 ‐10 ‐6 mol/L) inhibit reabsorption. Similar dose‐response relations have been obtained for luminal and peritubular addition of AIL 3. The cellular responses to All are mediated via an AT‐1 receptor coupled via G‐regulatory proteins to several parallel signal transduction pathways. Low doses inhibit the basolateral adenylate cyclase, lower intracellular cAMP and withdraw the inhibitory effect of protein kinase A on the luminal Na/H exchanger. Stimulation of this exchanger may also occur due to All‐receptor activation of phospholipase C to release diacyl glycerol, or by local transduction in the brush‐border membrane involving phospholipase A 2 . 4. Inhibition of proximal fluid reabsorption is associated with increased intracellular Ca 2+ released from intracellular stores, or entering via voltage‐sensitive channels in response to the release of inositol‐l,4,5,‐trisphosphate, or following Ca 2+ channel opening induced by the arachidonic acid metabolite 5,6,‐epoxy‐eicosatrienoic acid. 5. The stimulatory actions of peritubular All on proximal transport are inhibited by physiological concentrations of atrial natriuretic factor (ANF) and by parathyroid hormone (PTH). 6. It is concluded that intrarenal All acts to maintain optimal matching of fluid reabsorption and filtered load in response to changes in sodium balance, as well as to promote acidification of the urine during acidosis and perhaps to potentiate tubular growth following renal injury.