Endothelium-independent conversion of angiotensin I by vascular smooth muscle cells

The conversion of angiotensin I (AT-I) to angiotensin LT. (AT-II) by angiot ensin I-converting enzyme (ACE) is a key step in the action of angiotensins . ACE is constitutively expressed in endothelial cells, but can also be det ected at low levels in smooth muscle cells (SMC). Furthermore, in rats the ACE activity can be induced in SMC in vivo by experimental hypertension or vascular injury and in vivo by corticoid treatment. This study was therefor e undertaken to evaluate the conversion of AT-I and its subsequent effects in SMC in basal conditions and after stimulation by dexamethasone. Using ra t and human SMC, showed that dexamethasone induced ACE expression and that this enzyme was functional, leading to AT-II-dependent intracellular signal ing. A fourfold increase in phospholipase C activity in response to AT-I wa s observed in dexamethasone-activated SMC compared with quiescent SMC. This effect of dexamethasone on signal transduction is dependent on ACE activit y, whereas AT-II receptor parameters remain unchanged. The action of AT-I w as blocked by an AT, receptor antagonist, suggesting that it was mediated b y AT-II. Similarly, dexamethasone-induced ACE expression was present in hum an SMC, and calcium signaling was mobilized in response to AT-I in activate d human cells. Experiments performed with cocultures of endothelial cells a nd SMC in a Transwell system showed that the response to AT-I was limited t o the compartment where AT-I was localized, suggesting that AT-I does not p ass through the endothelial cell barrier to interact with underlying SMC. O ur data suggest that in rat, as in human SMC, the conversion of AT-I into A T-II and the signal transduction in response to AT-I are ACE expression-dep endent. In addition, the present findings show that this SMC response to AT -I is endothelium-independent, supporting the idea of a local generation of AT-II in the vascular wall.