Abstract

Recent reports have shown that cultured endothelial cells release into the culture medium a substance (or substances) that contracts isolated preparations of arterial smooth muscle [endothelial-derived constrictor factor (EDCF)]. To evaluate the coronary and cardiac effects of EDCF, isolated rabbit hearts retroperfused in a nonrecirculating system with Krebs-Henseleit solution were challenged with bolus injections (100-600 microliter) of either serum-free minimum essential medium (vehicle) or aortic endothelial cell supernates concentrated in minimum essential medium (EDCF). EDCF, but not its vehicle, produced dose-dependent coronary vasoconstriction unaccompanied by changes in left ventricular contraction or heart rate. The constrictor responses were remarkably well sustained with little or no decrement in resistance occurring over a 15-min observation period. Nitroprusside inhibited the development of and reversed on-going vasoconstriction evoked by EDCF. Neither meclofenamate nor diethylcarbamazine influenced EDCF-induced pressor responses, thereby negating a role for arachidonic acid metabolites. Coronary vasoconstriction induced by EDCF also was unaffected by blockade of alpha-adrenergic, histaminergic or serotonergic receptors. Incubation of EDCF with trypsin attenuated the pressor effects markedly, suggesting that EDCF may be a peptide. Roles for angiotensin or substance P were ruled out, however, as saralasin failed to influence EDCF-induced constriction and since substance P was inactive in the perfused rabbit heart preparation. We conclude that a substance (or substances), probably a peptide, released from cultured endothelial cells provokes sustained coronary vasoconstriction by an unknown mechanism.