Major role of the renin angiotensin system in the neointima formation after vascular injury in guinea pigs.
ACE inhibition has been shown to prevent neointima formation after vascular injury. However, it is not known if this effect is due to a specific inhibition of the renin angiotensin system or to another mechanism such as the accumulation of bradykinin. In order to answer this question we compared the effects of maximal effective doses of cilazapril, an angiotensin converting enzyme (ACE) inhibitor, and ciprokiren, a new renin inhibitor, in guinea pigs. Vascular injury was induced by endothelial denudation of the right carotid artery of guinea pigs treated either by saline (control group), cilazapril (30 mg/kg/day) or ciprokiren (24 mg/kg/day). Twelve days after the ballooning, the guinea pigs were sacrificed, the carotid arteries were perfused fixed and neointima formation was evaluated by quantitative morphometry. Both, ciprokiren and cilazapril prevented neointima formation to the same extent (inhibition by 42 and 49%, respectively, p < 0.05). These results suggest that, in guinea pigs, renin inhibition prevents neointima formation to a similar extent as ACE inhibition. Therefore, ACE inhibitors seem to act in this model by inhibiting the renin angiotensin system and not by other effects such as accumulation of bradykinin.
Clozel
J P
JP
Pharma Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Hess
P
P
Schietinger
K
K
Breu
V
V
Fischli
W
W
Baumgartner
H R
HR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries; D002404:Catheterization; D017315:Cilazapril / Q000494:pharmacology*; D006168:Guinea Pigs; D007093:Imidazoles; D012083:Renin / Q000097:blood / Q000494:pharmacology; D012084:Renin-Angiotensin System / Q000187:drug effects*; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology; D000092502:Renin Inhibitors
D017315:Cilazapril; D007093:Imidazoles; D012083:Renin; D000092502:Renin Inhibitors; C085570:ciprokiren