The production of cyclic GMP decreases with the coronary endothelial dysfunction after heart transplantation

Abstract

A porcine model of heterotopic heart transplantation without immunosuppression was used to assess the mechanisms underlying the coronary endothelial dysfunction leading to coronary graft vasculopathy. Vascular reactivity studies showed a selective endothelial dysfunction to Giproteins mediated agonists thirty days after transplantation which became generalized to other pathways at sixty days. There was a progressive increase in the coronary intimal thickening in allografts from day thirty to day sixty. The addition of L-arginine (5mM) at the time of organ chambers experiments did not improve the endothelium-dependent relaxations to pertussis toxin-sensitive agonists. The basal production of cyclic guanosine monophosphate (GMP) was compared in native and allograft coronary arteries sixty days after transplantation. There was a statistically significant decrease of cyclic GMP release from the allograft coronary arteries compared to native arteries. This decrease in cyclic GMP is consistent with a decreased release or an increased degradation of nitric oxide underlying the coronary endothelial dsyfunction after heart transplantation Decreased availability of nitric oxide may contribute to graft coronary vasculopathy by favoring activation of adhesion molecules, platelet aggregation and proliferation of vascular smooth muscle cells.