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, 12-0-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 x 10-7M) causes only a transient contractile response, while PE (10-5M) 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, indicating the 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 inability of AII to maintain tension, unlike PE, is due to its inability to produce DAG continuously and activate protein kinase C