Angiotensin II desensitization and Ca2+ and Na+ fluxes in vascular smooth muscle cells

The role of ion fluxes in angiotensin II (AII) desensitization (tachyphylaxis) was investigated by studying Na⁺ and Ca²⁺ translocation in cultured vascular smooth muscle cells from the rat aorta. The effects of AII were compared to those of [1-sarcosine]-AII (Sar¹-AII), an analogue which also induces tachyphylaxis, and [2-lysine]-AII (Lys²-AII), an analogue that does not show this property. Maximally effective concentrations of the three peptides induced a rapid and transient increase in ⁴⁵Ca²⁺ efflux, a rapid and sustained decrease in total cell Ca²⁺ and an increased Na⁺ permeability. Repeated treatments, at short intervals, with either of the three peptides abolished the effect on Ca²⁺ efflux, and this desensitization was slowly reversible. A 30-min rest period was sufficient for full recovery of the response of cells that were desensitized by Lys²AII, whereas the recovery from AII or Sar¹AII-desensitization was still not complete after 60 min. Our results suggest that the difference in the behaviour of the tachyphylactic AII and Sar¹-AII and the non-tachyphylactic Lys²-AII lays not in the production of different signals upon binding to the receptor, but in a difference in the hormone-receptor interaction itself.