ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS REDUCE NEOINTIMAL THICKENINGAND MAINTAIN ENDOTHELIAL NITRIC-OXIDE FUNCTION IN RABBIT CAROTID ARTERIES

Application of periarterial collars induced atheroma-like lesions in t he carotid arteries of normocholesterolemic rabbits. Vessel segments t aken from the mid-region of the collar (cuffed region) and control reg ions of the same artery were studied at 7 days after surgery. A group of placebo rabbits was provided ad libitum with regular tap water, and treated animals were supplied for 14 days (beginning 7 days before co llar application) with water containing perindopril (daily intake of a pproximately 0.3 mg/kg). Perindopril treatment reduced plasma angioten sin-converting enzyme (ACE) activity by 88%, but did not significantly alter arterial blood pressure or heart rate. The sensitivity of arter ial rings to angiotensins I and II did not differ between control and cuffed arteries in either placebo or perindopril-treated rabbits, but in rings from both groups of rabbits the sensitivity to the vasoconstr ictor action of serotonin was higher in the cuffed segments, as in pre vious studies. In addition, in placebo rabbits the endothelium-depende nt vasorelaxant response to acetylcholine (which results from the rele ase of nitric oxide) was weaker in cuffed arteries than in controls, w hereas in the perindopril-treated animals, this impairment of relaxati on was restored to the extent that, in cuffed vessels, it was no longe r significantly different from the controls. Similar results were obta ined in rabbits treated with another ACE inhibitor (ramipril). In cont rast, acute treatment with the metabolite, perindoprilat, in vitro (1. 0 mu M) did not alter the response to acetylcholine in control or cuff ed rings from placebo rabbits. Morphologically, vessel segments taken from the center of the cuffed artery of placebo rabbits showed a thick ened intima with marked smooth muscle cell proliferation. The intimal/ medial cross-sectional area ratio was reduced from 0.11 +/- 0.02 (n = 10) in placebo rabbits to 0.05 +/- 0.01 (n = 5) in perindopril-treated rabbits. Thus inhibition of ACE with perindopril reduces intimal thic kening and partially restores the defective vasodilation induced by en dothelial cell release of nitric oxide.