Effect of converting enzyme inhibition on allograft-induced arterial wall injury and response.
Converting enzyme inhibition (CEI) can prevent myointimal proliferation after arterial wall balloon injury. Because intimal proliferation is the main long-term complication of chronic vascular rejection, we tested the effect of CEI (perindopril, 1 mg/kg twice a day) on arterial rejection-induced intimal proliferation, using a model of aortic allograft in normotensive Wistar-Kyoto and spontaneously hypertensive rats. Eight-week-old rats were grafted and studied 2 months later. The structural parameters of the transplanted aortic wall were measured by morphometric analysis of specifically stained, formol-fixed sections. CEI did not prevent adventitial inflammatory infiltration but significantly increased the number of living cells and prevented the partial destruction of elastic laminae in the media, thereby increasing medial thickness to close to that of sham-operated controls. CEI significantly decreased intimal thickness and intimal collagen density, without changing the absolute number of intimal smooth muscle cells. The intimal thickness and the intimal collagen density were significantly correlated with the effect of CEI on blood pressure. CEI partially prevented the consequences of immune injury to the media within the arterial wall, probably by suppressing the proinflammatory activity of angiotensin II. It also decreased the recipient arterial wall response by acting more on the trophicity of intimal cells and on their ability to produce collagen rather than by directly inhibiting smooth muscle cell proliferation in our model of arterial allograft.
INSERM Unit 36, Lariboisière Hospital, Paris, France.
D
D
Plissonnier
G
G
Amichot
M
M
Duriez
J
J
Legagneux
B I
BI
Levy
J B
JB
Michel
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000473:pathology / Q000637:transplantation*; D002455:Cell Division; D003094:Collagen / Q000032:analysis; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D020913:Perindopril; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014184:Transplantation, Homologous
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D003094:Collagen; D020913:Perindopril