Oral cicaprost protects from hypercholesterolaemia-induced impairment of coronary vasodilation

Isolated Langendorff-hearts prepared from cholesterol fed rabbits (1% cholesterol for 3 months) showed a significant impairment in endothelium-dependent relaxation after short-term infusion of bradykinin (0.05 mumol/l) and carbamoylcholine (0.1 mumol/l). Generation of the endothelial mediators nitric oxide and prostacyclin by bradykinin was enhanced in hypercholesterolemia. Cicaprost treatment (5 micrograms/kg x d) largely prevented the hypercholesterolemia-related impairment of coronary vasodilation and nitric oxide release. It is concluded that (i) impairment of endothelium-dependent relaxation in the coronary microcirculation of hypercholesterolemic rabbits is not due to diminished endothelium-dependent mediator release but rather to accelerated inactivation or reduced activity of the released mediators and that (ii) oral cicaprost beneficially influence these alterations.