Acute desensitization to angiotensin II: Evidence for a requirement of agonist-induced diacylglycerol production during tonic contraction of rat aorta

A possible role for protein kinase C during the tonic phase of arterial contraction was examined in rat aorta by observing the effects of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), on angiotensin II (AII)-induced responses. The ability of AII and phenylephrine (PE) to induce diacylglycerol (DAG) production was monitored as agonist-stimulated 32P-labelling of phosphatidic acid (PA). AII (5 × 10-7 M) causes only a transient contractile response, while PE (10-5 M) causes a sustained tonic contraction. 32P-labelling studies showed that AII caused an initial increase of PA synthesis equal to PE, however, AII failed to sustain this increase at 5 and 10 min while PE was able to do so. This indicates a failure of AII to provide DAG to sustain protein kinase C activation. Activation of protein kinase C with TPA prior to and during AII exposure converted the normally transient contraction to a more sustained, tonic pattern. These results suggest that the capacity of neuroendocrine agonists to maintain tension is due to their ability to produce DAG continuously and thereby activate protein kinase C.