Effects of bosentan on neointimal response following coronary angioplasty.
BACKGROUND
Endothelins are important vasoconstrictors and cellular-growth promoters. ETA-specific antagonists have been shown to reduce neointimal response to injury in some experimental angioplasty models. However, there is little information on the effects of dual ETA/ETB receptor blockers, such as bosentan, on neointimal proliferation following experimental coronary angioplasty.


METHODS
Coronary injury was achieved by directional atherectomy in the left anterior descending artery of 20 pigs. Animals were randomly assigned to receive a daily dose of oral bosentan (30 mg kg-1) (group I, n = 10) or no treatment (group II, n = 10). At 4 weeks, arteries were processed for histomorphometry and endothelin characterization.


RESULTS
Vessel injury score was similar among the two groups. Overall, a linear correlation was found between injury and neointimal development (r = 0.57, P = 0.01). This correlation had a lower slope in group I compared with group II (P < 0.001), indicating a smaller amount of neointimal development for a similar degree of injury in bosentan-treated animals. Multivariate regression showed that neointimal response was reduced by oral treatment with bosentan (beta: -0.59 mm2, 95% CI: -1.11/-0.06 mm2). In addition, immunostaining revealed fewer positive endothelin areas in group I arteries.


CONCLUSIONS
Oral treatment with bosentan reduces neointimal development following coronary angioplasty in this experimental model.
Sanmartín
M
M
Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain. marcelo.sanmartin.fernandez@sergas.es
Fernández-Ortiz
A
A
Fantidis
P
P
Aragoncillo
P
P
Fernández-Durango
R
R
Rollín
R
R
Alfonso
F
F
Hernández
R
R
Escaned
J
J
Macaya
C
C
D000284:Administration, Oral; D017130:Angioplasty / Q000379:methods*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000077300:Bosentan; D023903:Coronary Restenosis / Q000209:etiology / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects*; D004195:Disease Models, Animal; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000032:analysis; D006439:Hemodynamics / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D013552:Swine; D017539:Tunica Intima / Q000187:drug effects*
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D013449:Sulfonamides; D000077300:Bosentan