Angiotensin Tachyphylaxis and its Reversal

Abstract

Tachyphylaxis to angiotensin and some analogues has been demonstrated on spirally cut arterial strips from cat, dog, sheep and rat, and on venous strips from rabbit and cat. Rabbit and guinea pig arteries do not appear to become tachyphylactic. A free C-terminal carboxyl group of angiotensin is necessary for binding with receptor sites and development of tachyphylaxis. Tachyphylaxis seems to represent saturation of receptor sites. It can be reversed by plasma fractions rich in angiotensinase A, possibly by metabolizing the N-terminal part of angiotensin directly from the bound state. Dowex 50 can also reverse it, probably by physical adsorption and stronger binding of angiotensin. Angiotensinase A does not metabolize βaspartyl¹-angiotensin and does not reverse tachyphylaxis to this peptide. A possible scheme of interaction between peptide and receptor site is presented.