Effects of chronic ACE inhibition on cardiac hypertrophy and coronary vascular reserve in spontaneously hypertensive rats with developed hypertension.
Left ventricular hypertrophy due to hypertension is associated with a decrease of coronary vascular reserve. We have previously shown that chronic angiotensin converting enzyme (ACE) inhibition prevents cardiac hypertrophy and improves coronary vascular reserve when the treatment is started before appearance of hypertension in spontaneously hypertensive rats (SHR). However, the effects of starting chronic ACE inhibition when hypertension was already developed is not known. The goal of the present study was to assess the effects of chronic ACE inhibition on coronary vascular reserve and on the morphology of the coronary microvasculature when treatment was started after hypertension had developed. For this purpose, one group of SHR was treated from 3-8 months of age with cilazapril, a new ACE inhibitor, and compared with a group treated by placebo. At the end of treatment, cardiac hypertrophy, coronary vascular reserve, density and cross-sectional surface area of the myocardial capillaries (normalized for the myocardial mass) and wall/lumen ratio of the coronary arterioles were determined. Chronic ACE inhibition with cilazapril reduced cardiac hypertrophy and improved by more than 50% coronary vascular reserve in the left and right ventricles. In the left ventricle, the improvement was more pronounced in the subendocardium than in the subepicardium. Cilazapril increased the density and the cross-sectional surface area of the myocardial capillaries and decreased the wall/lumen ratio of the arterioles of the left ventricle. We conclude that chronic ACE inhibition can improve coronary vascular reserve, increase capillary density and capillary cross-sectional surface area and decrease the thickness of the media of coronary arterioles in SHR even when treatment is started after development of hypertension.
Clozel
J P
JP
Pharmaceutical Research Department, F. Hoffmann-La Roche & Co., Ltd., Basel, Switzerland.
Kuhn
H
H
Hefti
F
F
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D006332:Cardiomegaly / Q000517:prevention & control*; D017315:Cilazapril; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000473:pathology; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000473:pathology; D011724:Pyridazines / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D017315:Cilazapril