Further studies on angiotensin tachyphylaxis.

Rabbit aorta and rat fundus do not display tachyphylaxis to angiotensin II (Asp1)angiotensin II) at 37 degrees C. These tissues do, however, display tachyphylaxis to [Sar1]angiotensin II (N-methylglycine 1 angiotensin II) and [dimethylglycine angiotensin II, respectively, at this temperature. At 22 degrees C, both tissues displayed rapid tachyphylaxis to [Asp1]angiotensin II which was reversed on prolonged incubation in peptide-free medium. At 37 degrees C, but at a lower than normal pH (pH 6.5 instead of 7.4), the rabbit aorta developed rapid tachyphylaxis to [Asp1)angiotensin II; this effect also was reversed on prolonged incubation in peptide-free medium. The rat uterus, at 30 degrees C, displayed tachyphylaxis to [Asp1]angiotensin II and analogs in order of rate of onset: [Sar1]angiotensin II greater than [Asp1]angiotensin II greater than [des-Asp1]angiotensin II. Over half of the individual uterine strips tested displayed no tachyphylaxis to [des-Asp1]angiotensin II. However, at 22 degrees C tachyphylaxis to all three compounds was rapid on onset and was reversed on prolonged incubation. The results indicate a correlation between affinity of the peptide analog for angiotensin receptor and its ability to induce tachyphylaxis. A possible involvement of membrane-bound enzymes in the onset and duration of tachyphylaxis is suggested.