784-2 Coronary Vasomotor Responses in Cyclosporine-Treated Piglets

Abstract

Chronic treatment with cyclosporine (Cx) seems to produce a decreased ability of the endothelium to secrete nitric oxide. However, its effect on the coronary arterial system remains controversial. Therefore, coronary arteries isolated from piglets treated for 3 weeks with Cx (10 mg/kg/day I.M.; group 1) were studied in organ baths and compared to those isolated from control animals (I.M. injections of the Cx solvent, group 2). On rings contracted with prostaglandin F 2α (PGF 2α ), the endothelium-dependent relaxations to serotonin (5HT, 1 nM to 0.3 μM; in the presence of ketanserin 1 μM), bradykinin (BK, 1 nM to 0.1 μM) , substance P (SP’ 0.1 nM to 10 nM) and calcium ionophore (A23187, 1 nM to 1 μM) were assessed: Group Area under curve (AUC) 5HT BK SP A23187 1 (n = 12) 479 ± 24 * 158 ± 18 * 198 ± 8 * 217 ± 10 * 2 (n = 12) 385 ± 22 55 ± 17 145 ± 12 224 ± 18 mean ± SEM * P < 0.02 vs group 2 the maximal relaxation was significantly decreased only for BK (76 ± 4% vs 92 ± 4%, % of PGF 2α -induced plateau). Depolarization-induced contractions (KCI 90 mM) were similar in both groups whereas the acetylcholine (Ach)-induced contractions (% of KCI 90 mM) were enhanced: the AUC in group 1 was 245 ± 51 versus 110 ± 15 in group 2 (P < 0.01). After mechanical removal of the endothelium, the increased responsiveness to Ach persisted in group 1. Thus, chronic exposure to Cx impairs receptor-mediated endothelium-dependent relaxations in coronary arteries and also produces functional changes in smooth muscle cells. These alterations may playa role in the occurrence of cardiac graft vasculopathy.