Influence of the status of the renin-angiotensin system on the effect of cilazapril on neointima formation after vascular injury in rats.
BACKGROUND
Angiotensin converting enzyme (ACE) inhibition has been shown to prevent neointima formation after vascular injury in rats. However, clinical results evaluating restenosis after angioplasty have been negative. The goal of the present study was to evaluate the influence of the renin-angiotensin system (RAS) status on the effect of ACE inhibition on neointima formation.


RESULTS
Arterial injury was produced by ballooning the left carotid artery of rats, and neointima formation was evaluated by morphometry 2 weeks after ballooning. The effects of cilazapril were assessed in four experimental groups: normotensive rats, spontaneously hypertensive rats, hypertensive rats with a renal artery stenosis induced by clipping (two-kidney, one-clip rats), and hypertensive rats with uninephrectomy, high salt intake, and administration of deoxycorticosterone (DOCA). In parallel groups of rats, measurement of plasma renin activity was made in order to characterize (at least at the plasma level) the status of the RAS. As expected, renal artery stenosis markedly increased plasma renin activity, and DOCA decreased it to undetectable levels. Cilazapril had a marked preventive effect on neointima formation in normotensive rats, spontaneously hypertensive rats, and two-kidney, one-clip rats but was ineffective in DOCA rats.


CONCLUSIONS
We conclude that the status of the RAS has a major influence on the effect of cilazapril on neointima formation after vascular injury.
Clozel
J P
JP
Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Müller
R K
RK
Roux
S
S
Fischli
W
W
Baumgartner
H R
HR
D000818:Animals; D020212:Carotid Artery Injuries; D016893:Carotid Stenosis / Q000503:physiopathology / Q000517:prevention & control*; D017315:Cilazapril / Q000627:therapeutic use*; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000502:physiology*; D017539:Tunica Intima / Q000187:drug effects*
D017315:Cilazapril; D003900:Desoxycorticosterone