New approaches to the study of angiotensin tachyphylaxis.

Of the various mechanisms proposed to explain the development of tachyphylaxis, the initial step of drug-receptor interaction has received the most attention. The present study suggests that the affinity of angiotensin II itself or an angiotensin analogue for the angiotensin receptor is a determing factor in the development of tachyphylaxis. The concept of negative cooperativity is introduced as a consequence of the observed correlation in the present study between slopes of less than unity as determined in Hill plots and the development of tachyphylaxis.