Abstract
Background A marked decline in vascular myogenic response occurs during the course of rat cardiac allograft rejection. Two important contributory features are an inducible nitrous oxide synthase (iNOS)-catalyzed, NO-mediated vasodilation and a loss of smooth muscle function. In this study, we examine the effect of cyclosporine immunosuppressive therapy on the alleviation of arterial dysfunction of coronary resistance arteries in allografts using pressure myography. Methods Rats receiving heterotopic abdominal cardiac transplantation were treated with cyclosporine (5 mg/kg), Cremophore or distilled water. Coronary septal arteries (internal diameter 200 μm) were dissected from isograft (Lewis to Lewis) and allograft (Fisher to Lewis) rat hearts at Day 21 post-transplantation and mounted on a pressure myograph. Pressure-induced vasoconstriction was measured before and after iNOS inhibition with aminoguanidine (AG; 100 μmol/liter). Both endothelium-based (ACh-induced) and endothelium-independent (sodium nitroprusside–induced) vasorelaxation were also recorded in each group. Results Pressure-induced myogenic contraction was reduced in allograft coronary arteries at Day 21 post-transplantation compared with matched isografts ( p < 0.05). AG potentiated myogenic tone in allograft arteries, but had no effect on untreated Day 21 isograft vessels, indicating the presence of iNOS-based relaxation only in allograft vessels. Depolarization-induced vasoconstriction was lower in allograft compared with isograft arteries ( p < 0.05). Cyclosporine therapy also improved depolarization-induced constriction in allograft vessels compared with untreated groups ( p < 0.05). Furthermore, cyclosporine therapy preserved endothelium-based and endothelium-independent vasorelaxation in allograft arteries at Day 21 post-transplantation. Conclusions Cyclosporine immunosuppressive therapy has a significant effect on the alleviation of early endothelial and smooth muscle dysfunction in coronary allograft arteries.
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