Sustained coronary vasoconstriction provoked by a peptidergic substance released from endothelial cells in culture.
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.
Gillespie
M N
MN
Owasoyo
J O
JO
McMurtry
I F
IF
O'Brien
R F
RF
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001679:Biogenic Amines / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects*; D004727:Endothelium / Q000378:metabolism*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011968:Receptors, Histamine / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology; D013373:Substance P / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D001095:Arachidonic Acids; D001679:Biogenic Amines; D010455:Peptides; D011942:Receptors, Adrenergic, alpha; D011968:Receptors, Histamine; D011985:Receptors, Serotonin; D014662:Vasoconstrictor Agents; D009599:Nitroprusside; D016718:Arachidonic Acid; D013373:Substance P; D008469:Meclofenamic Acid