ET(A)/ET(B) receptor antagonist bosentan inhibits neointimal development in collared carotid arteries of rabbits.
The contribution of endothelin to the genesis of neointimal development in collared rabbit carotid arteries, a widely accepted model of atherosclerosis, was investigated. Three sets of rabbits were studied. In the first group, a non-occlusive, biologically inert silastic collar was positioned around the right carotid artery of the rabbit. In another group, the application of the collar was accompanied by endothelial denudation via a Fogarty arterial balloon catheter, while the third group of animals underwent only endothelial denudation. After two weeks, intimal hyperplasia of a similar degree was observed in all groups. The administration of the nonselective ET(A)/ET(B) receptor antagonist Bosentan, significantly reduced both the neointimal area and the intima/media area ratio in all groups. However, the beneficial effects of Bosentan were less pronounced in balloon injured vessels than in collared ones. The results of the present study indicate that i) endothelin has a key role in the development of intimal hyperplasia following arterial collaring, ii) the contribution of endothelin to intimal hyperplasia is greater in collared arteries that in balloon injured ones, and iii) the nonselective ET(A)/ET(B) receptor antagonists are potential tools for the prevention of intimal hyperplasia.
Marano
G
G
Laboratorio di Farmacologia, Istituto Superiore di Sanità, Rome, Italy. gmarano@net.iss.it
Palazzesi
S
S
Bernucci
P
P
Grigioni
M
M
Formigari
R
R
Ballerini
L
L
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D000077300:Bosentan; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology*; D065128:Endothelin Receptor Antagonists; D006965:Hyperplasia / Q000473:pathology / Q000517:prevention & control; D008297:Male; D009389:Neovascularization, Pathologic / Q000473:pathology* / Q000517:prevention & control*; D011817:Rabbits; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013449:Sulfonamides / Q000494:pharmacology*
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013449:Sulfonamides; D000077300:Bosentan