Peptide 6A, a fibrin(ogen) degradation product, increases coronary blood flow.
The coronary hemodynamic effects of intracoronary administration of a fibrin(ogen)-derived pentapeptide, Ala-Arg-Pro-Ala-Lys (peptide 6A), were evaluated in open-chest anesthetized dogs. With administration of peptide 6A (2.5-30 mumol), coronary blood flow increased and coronary vascular resistance decreased promptly in a dose-related manner. Increase in coronary blood flow was independent of any change in indexes of myocardial O2 demand, indicating the peptide 6A exerts direct effects on coronary arterial tone. Systemic arterial and left ventricular end-diastolic pressures remained unchanged with smaller doses but decreased when higher doses of peptide 6A (greater than or equal to 20 mumol) were administered. Plasma concentrations of 6-ketoprostaglandin F1 alpha, stable hydrolysis product of prostacyclin, increased in coronary sinus blood samples in conjunction with increase in coronary blood flow. Administration of indomethacin (5 mg/kg iv) inhibited peptide 6A-induced release of prostacyclin and significantly attenuated the effects of peptide 6A on coronary hemodynamics. Pretreatment of animals with H2-receptor blocker cimetidine (500 mg iv) or with H1-and H2-receptor blocker diphenhydramine (50 mg iv) had no significant effects on peptide 6A-induced increase in coronary blood flow. This study suggests that this fibrin(ogen)-derived peptide has potent vasodilator effects on the coronary vascular bed of the dog, and these effects are in part mediated by stimulation of prostacyclin release.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D005338:Fibrin Fibrinogen Degradation Products / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*
D000596:Amino Acids; D005338:Fibrin Fibrinogen Degradation Products; C026893:fibrinogen peptide 6A; D015121:6-Ketoprostaglandin F1 alpha; D007213:Indomethacin