Spirapril prevents left ventricular hypertrophy, decreases myocardial damage and promotes angiogenesis in spontaneously hypertensive rats.
To test whether angiotensin-converting enzyme (ACE) inhibition may prevent myocardial damage and may affect coronary microvasculature in spontaneously hypertensive rats (SHR), young 5-week-old SHR were treated for 3 months with spirapril and changes in blood pressure (BP) were monitored. Untreated SHR were used as controls. The rats were killed; left ventricular (LV) shape, weight, and wall thickness were examined and the ventricular myocardium was analyzed morphometrically to determine the effect of the drug on the relative amount, number per unit area of myocardium, and average dimension of foci of myocardial scarring. Moreover, volume fraction, surface, numerical density, and diffusion distance for oxygen of the coronary capillaries were analyzed. BP remained 20-30% lower in treated SHR with respect to controls, and LV weight and thickness decreased 20 and 21%, respectively. The number and dimension of the foci of fibrosis were reduced, resulting in an overall 68% decrement in the amount of myocardial damage. Finally, a 28% increment in numerical density of capillary profiles associated with a 13% reduction in their cross-sectional area decreased the diffusion distance for oxygen from the capillary wall to the myocytes by 14% in treated SHR. Spirapril decreases BP and LV weight and thickness in the SHR model of hypertension and substantially improves coronary capillary microvasculature, decreasing hypertensive myocardial damage. These results may be attributed to inhibition of the systemic effects of angiotensin II (AII) as well as to a local protective action of the drug against possible intramyocardial AII production.
Olivetti
G
G
Department of Pathology, University of Parma, Italy.
Cigola
E
E
Lagrasta
C
C
Ricci
R
R
Quaini
F
F
Monopoli
A
A
Ongini
E
E
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000254:growth & development; D003331:Coronary Vessels / Q000187:drug effects / Q000254:growth & development; D004656:Enalapril / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005355:Fibrosis / Q000188:drug therapy; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; C052555:spirapril