EFFECTS OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION WITH PERINDOPRIL ON HEMODYNAMICS, ARTERIAL STRUCTURE, AND WALL RHEOLOGY IN THE HINDQUARTERS OF ATHEROSCLEROTIC MINIPIGS

The effects of ACE inhibition with perindopril on the atherosclerosis- induced impairment of arterial flow were investigated via histopatholo gic studies, hemodynamics, and vascular rheology of hindlimb arteries in 7 adult Pitman-Moore mini-pigs (7 months of age) fed for 4 months w ith an atherogenic diet and perindopril (at the daily oral dose of 4 m g, which induced a continuous 70% inhibition of serum ACE activity), v ersus 7 atherogenic and 7 control animals. Major fibroproliferative fa tty lesions with medial intimalization were observed in the abdominal aorta. Atherosclerosis impaired the function of both capacitance and r esistance hindlimb arteries. In atherogenic mini-pigs, blood pressure (BP) increased significantly due to increased hindlimb peripheral resi stance (HPR) and aortic input impedance, although aortic blood flow wa s not affected. Altered aortic wall rheology revealed that the stiffne ss of the aorta was markedly increased due to increased wall tension a nd reduced viscoelasticity, the viscous component being reduced in the arterial wall. Perindopril significantly opposed these alterations by reducing BP, HPR and input impedance and by returning parietal stiffn ess to control values by increasing aortic compliance. Angiotensin con verting enzyme (ACE) inhibition significantly prevented the developmen t of atherosclerosis in the abdominal aorta by decreasing the cross-se ctional area of lesions and the presence of lipid-laden cells, as well as by preventing alteration and fragmentation of elastic laminae. In conclusion, ACE inhibition with perindopril showed a significant preve ntive action on atherosclerosis-induced deleterious effects on vascula r wall function and structure in mini-pig arteries.