Vascular protection with cilazapril.
The hypertrophy of the media of coronary arteries associated with hypertension reduces cross-sectional area and limits vascular reserve. Cilazapril 10 mg/kg daily decreased cardiac hypertrophy, and decreased minimal coronary vascular resistance by 40% when administered to spontaneously hypertensive rats (SHR) at the onset of hypertension. After hypertension had developed, cilazapril restored arterial pressure to normal and increased the maximal coronary blood flow in isolated perfused hearts by 96%, which was probably a result of a marked decrease in medial hypertrophy of the coronary arteries. Similarly, cilazapril improved cerebral vascular reserve in the mesenteric and renal arteries of SHR. In the rat model of vascular injury produced by ballooning, cilazapril 10 mg/kg daily demonstrated a marked preventive effect on the myointimal proliferation that resulted in untreated controls, a phenomenon responsible for restenosis in humans after arterial angioplasty. Although this effect occurred with usual antihypertensive dosages in rats, it appeared to be independent of the decrease in arterial pressure since effective antihypertensive dosages of verapamil did not prevent neointima formation. In view of the clinical potential for preventing restenosis after coronary angioplasty, 2 multicentre trials of cilazapril are ongoing to test this hypothesis.
Clozel
J P
JP
Department of Pharmaceutical Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Powell
J S
JS
Kuhn
H
H
Müller
R K
RK
Hefti
F
F
Baumgartner
H R
HR
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000473:pathology; D017315:Cilazapril; D006973:Hypertension / Q000150:complications; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011724:Pyridazines / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D014652:Vascular Diseases / Q000209:etiology / Q000517:prevention & control*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D017315:Cilazapril