| Autor: |
Dias, Juliana, Ferrão, Fernanda M., Axelband, Flavia, Carmona, Adriana K., Lara, Lucienne S., Vieyra, Adalberto |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Renal Physiology; Apr2014, Vol. 306 Issue 8, pF855-F863, 9p |
| Abstrakt: |
The physiological roles of ANG-(3-4) (Val-Tyr), a potent ANG II-derived peptide, remain largely unknown. The present study 1)investigates whether ANG-(3-4) modulates ouabain-resistant Na+-ATPase resident in proximal tubule cells and 2) verifies whether its possible action on pumping activity, considered the fine tuner of Na+ reabsorption in this nephron segment, depends on blood pressure. ANG-(3-4) inhibited Na+-ATPase activity in membranes of spontaneously hypertensive rats (SHR) at nanomolar concentrations, with no effect in Wistar- Kyoto (WKY) rats or on Na+-K+-ATPase. PD123319 (10-10 M) and PKA(5-24) (10-6 M), an AT2 receptor (AT2R) antagonist and a specific PKA inhibitor, respectively, abrogated this inhibition, indicating that AT2R and PKA are central in this pathway. Despite the lack of effect of ANG-(3-4) when assayed alone in WKY rats, the peptide (108 M) completely blocked stimulation of Na+-ATPase induced by 10-10 M ANG II in normotensive rats through a mechanism that also involves AT2R and PKA. Tubular membranes from WKY rats had higher levels of AT2R/AT1R heterodimers, which remain associated in 10-10 M ANG II and dissociate to a very low dimerization state upon addition of 10-8 M ANG-(3-4). This lower level of heterodimers was that found in SHR, and heterodimers did not dissociate when the same concentration of ANG-(3-4) was present. Oral administration of ANG-(3-4) (50 mg/kg body mass) increased urinary Na+ concentration and urinary Na+ excretion with a simultaneous decrease in systolic arterial pressure in SHR, but not in WKY rats. Thus the influence of ANG-(3-4) on Na+ transport and its hypotensive action depend on receptor association and on blood pressure. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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