Role of sodium ions in angiotensin tachyphylaxis in the guinea-pig ileum and taenia coli.

We have examined the responsiveness of the guinea-pig ileum and taenia coli to angiotensin (ANG) analogues that were previously shown to be either able ([1-sarcosine]-ANG, Sar1-ANG) or unable ([2-lysine]-ANG, Lys2-ANG) to induce tachyphylaxis in the ileum. The taenia coli, in which tachyphylaxis had not been previously shown to occur, was strongly tachyphylactic to Sar1-ANG, but not to Lys2-ANG. The contractile responses of the ileum, as well as the contractile and electrical (sucrose-gap) events in the taenia coli, in response to the two ANG analogues, were used to investigate the tachyphylactic phenomenon and the role of Na+ in the manifestation. Relaxation of the ileum and repolarizations of the taenia coli were faster after treatment with Lys2-ANG than after Sar1-ANG. In the tachyphylactic state, relaxation and repolarization after Sar1-ANG became as fast as after Lys2-ANG. In "low-Na+" (80 mmol/l) medium, as well as in ouabain-treated preparations, the responses of the ileum to ANG analogues were similar to those of tissues in the tachyphylactic state. Addition of Ca2+ to taenia coli preparations previously treated with the two ANG analogues in Ca2+-free medium, caused contractile and electrical responses only in the case of Sar1-ANG. It is proposed that ANG tachyphylaxis is due to changes at the level of the receptor causing increased Na+ permeability which leads to a decreased Na+ gradient across the cell membrane.