Sustained coronary vasoconstriction provoked by a peptidergic substance released from endothelial cells in culture

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 236; no. 2; p. 339
• Main Authors: Gillespie, M N, Owasoyo, J O, McMurtry, I F, O'Brien, R F
• Format: Journal Article
• Language: English
• Published: United States 01-02-1986
• Subjects: Animals; Arachidonic Acid; Arachidonic Acids - metabolism; Biogenic Amines - physiology; Blood Pressure - drug effects; Cells, Cultured; Coronary Vessels - drug effects; Endothelium - metabolism; Male; Meclofenamic Acid - pharmacology; Nitroprusside - pharmacology; Peptides - metabolism; Peptides - pharmacology; Rabbits; Receptors, Adrenergic, alpha - physiology; Receptors, Histamine - physiology; Receptors, Serotonin - physiology; Substance P - pharmacology; Vasoconstriction - drug effects; Vasoconstrictor Agents - pharmacology
• ISSN: 0022-3565

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.