Angiotensin-(3-8) [= Ang IV] binds to a novel Ang binding site (AT.) receptor) that is pharmacologically distinct from the Ang II type AT] and AT2 receptor. The AT4 receptor was recently shown to be present in the renal cortex and outer medulla. The present study examined the possible involvement of the AT4 receptor in the Ang regulation of proximal tubule (PT) Na+ transport. PTs were enzymatically dissociated from male Wistar rats, and ouabain-suppressible tissue O2 consumption (QO2) measured as an on-line integrated index of transcellular PT Na+ transport. All PTs were treated with nystatin (Na+ ionophore) to maximally stimulate Na+ transport activity Ang II, Ang-(l-7) and Ang IV (each 1 pM) inhibited QO2 ∼9.2 nmol O2/min/mg protein. Pre-incubating PTs with 1 u,M DiValinal Ang IV (putative AT4 receptor antagonist) did not alter basal QO2 nor the response to nystatin or Ang II, yet attenuated the Ang-(1-7) response -75% and abolished the Ang IV response. PTs pre-treated with 1 μM losartan (AT1 receptor antagonist) attenuated the Ang II response -50%, the Ang-(1-T) response ∼25% without altering the Ang IV response. These data suggest the presence of the AT4 receptor in the rat proximal tubule and its involvement in the regulation of PT Na+ transport by Ang-(1-7) and Ang IV.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology