Effect of antiproliferative agents on vascular function in normal and in vitro balloon-injured porcine coronary arteries.

Local infusion of antiproliferative agents following coronary balloon angioplasty is used in vivo. This study examined the effects of the antiproliferative agents paclitaxel (5-beta, 20-Epoxy-1,2-alpha,4,7-beta,10-beta,13-alpha-Hexahydroxy-Tax-11-en-9-one 4,10-Diacetate 2_Benzoate 13-Ester with (2R,3S)-N-Benzoyl-3-Phenylisoserine; 10 and 50 microM), farnesyl protein transferase inhibitor III (FPT III, (E,E)-2-[2-Oxo-2-[(3,7,11-trimethyl-2,6,10-dodecatrienyl) oxy] amino] ethyl] phosphonic acid, (2,2-dimethyl-1-oxopropoxy) methyl ester, sodium); 10 and 25 microM), perillyl alcohol (4-isopropenyl-cyclohexenecarbinol; 1 and 2 mM) and Van 10/4 (Decahydro-1,1,4,7-tetramethyl-1H-cycloprop[e]azulen-4-o-[2-(3-methylpent-2-enoyl)-fucopyranoside]; 10 and 25 microM) on normal and in vitro balloon-injured porcine coronary arteries. Short-term (30 min) incubation had no effect on contraction or relaxation. Overnight incubation with 25 microM Van 10/4-attenuated contraction while perillyl alcohol abolished contractility completely. Endothelium-dependent relaxation was significantly attenuated by the higher concentration of paclitaxel, FPT III and Van 10/4. Stretch injury significantly enhanced sensitivity to 3-morpholinosydnonimine (SIN-1) while attenuating relaxation to calcimycin. Drug incubation (15 min) had no effect on these responses. In conclusion, paclitaxel, FPT III and Van 10/4 have no detrimental effects on vascular function after short-term administration to normal or stretch-injured arteries.