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.
Kennedy
Simon
S
Department of Physiology and Pharmacology, Strathclyde Institute of Biological Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, Scotland, UK. simon.kennedy@strath.ac.uk
Wadsworth
Roger M
RM
Wainwright
Cherry L
CL
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D052176:Azulenes; D000001:Calcimycin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D051231:Farnesyltranstransferase; D005643:Fucose / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D039821:Monoterpenes / Q000494:pharmacology; D063065:Organophosphonates / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
C436083:2-(2-oxo-2-((3,7,11-trimethyl-2,6,10-dodecatrienyl)oxy)aminoethyl)phosphonic acid, (2,2-dimethyl-1-oxopropoxy)methyl ester sodium; D000970:Antineoplastic Agents; D052176:Azulenes; D039821:Monoterpenes; D063065:Organophosphonates; D014662:Vasoconstrictor Agents; C488457:decahydro-1,1,4,7-tetramethyl-1H-cycloprop(e)azulen-4-o-(2-(3-methylpent-2-enoyl)fucopyranoside); D005643:Fucose; C032208:perillyl alcohol; D012701:Serotonin; D000001:Calcimycin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D017239:Paclitaxel