Prolongation of experimental cardiac allograft survival with thromboxane-related drugs.
A novel receptor antagonist, 3-hydroxymethyl-dibenzo (b,f) thiepin 5,5-dioxide (L-640,035) and the thromboxane synthase inhibitor, sodium (E) -3-(4-[3-pyridylmethyl phenyl]) -2-methyl-acrylate (OKY 1581) were evaluated for their effect in promoting the survival of cardiac allografts in Lewis rats that received cardiac allografts from Lewis x Brown-Norway F1 rats. Neither of these drugs or azathioprine alone significantly prolonged graft survival. However a combination of azathioprine with either of the two drugs significantly increased graft survival. Because L-640,035 inhibits platelet and smooth muscle responses to thromboxane-mimics, and because OKY 1581 is a specific thromboxane synthase inhibitor, we conclude that thromboxane may have a causal role in experimental cardiac allograft rejection in rats.
Foegh
M L
ML
Khirabadi
B
B
Ramwell
P W
PW
D000818:Animals; D001379:Azathioprine / Q000494:pharmacology; D003988:Dibenzothiepins / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000187:drug effects; D017482:Receptors, Thromboxane; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000502:physiology*; D014184:Transplantation, Homologous
D003988:Dibenzothiepins; D008689:Methacrylates; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013931:Thromboxanes; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; C041107:L 640035; D013930:Thromboxane-A Synthase; D001379:Azathioprine