The role of
angiotensin receptor subtypes 1 and 2 was assessed on
neointima formation after injury in rat carotid artery. The effects of
angiotensin converting enzyme inhibition by
perindopril (3 mg.kg-1 x day-1 p.o.) and selective blockade of
angiotensin subtype 1 receptors by
DuP 753 (5 and 30 mg.kg-1 x day-1 p.o.) were compared on proliferative response to balloon injury. In rats treated 6 days before and for 14 days after injury,
perindopril significantly reduced (-76%, p < 0.01) myointimal
hyperplasia. In contrast,
DuP 753 at 5 mg.kg-1 x day-1 did not modify the hyperplastic response to balloon catheterization. Only at 30 mg.kg-1 x day-1 was
DuP 753 able to reduce
neointima formation (-47%, p < 0.05). This dose was equipotent to
perindopril on the renin-angiotensin system as assessed by the pressor response to
angiotensin II and
angiotensin I. Therefore, blockade of subtype 1 receptors was a less effective means of suppression of myointimal growth than
angiotensin converting enzyme inhibition, suggesting that another
angiotensin receptor subtype or converting
enzyme substrates are involved in this process. For the determination of whether
angiotensin subtype 2 receptors were implicated, the specific subtype 2 receptor antagonist
CGP 42112A (1 mg.kg-1 x day-1) was continuously infused perivascularly for 14 days in the vicinity of the injured carotid artery.
CGP 42112A was as effective in preventing
neointima formation as
perindopril (-73%, p < 0.01, versus -76%, p < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)