Ramiprilat prevents PAF-induced myocellular and endothelial injury in a neutrophil-perfused heart preparation.
This study investigates the action of PAF-stimulated human polymorphonuclear leukocytes (PMN) on myocardial integrity and function in Langendorff-perfused guinea-pig hearts. Infusion of 10(6) PMN/ml resulted in a negative inotropic effect without larger biochemical evidence for myocardial tissue injury while infusion of PAF (1 microM) did not cause any permanent effect at all. However, the combined administration of PAF-stimulated PMN resulted in severely depressed myocardial contractile function and biochemical evidence for myocardial tissue injury. This was probably due to an enhanced uptake of PMN from the coronary perfusate and accumulation within the myocardial tissue. Ramiprilat, (10 microM) significantly improved left ventricular function and myocardial cell integrity. Similar results were obtained with bradykinin (1 nM). The data suggest a PAF-induced, PMN-mediated myocardial tissue injury as well as cardioprotective actions of ACE inhibition which are possibly related to stimulation of the kinin/prostacyclin axis.
Schrör
K
K
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, F.R.G.
Felsch
A
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D003402:Creatine Kinase / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D009504:Neutrophils / Q000502:physiology*; D010477:Perfusion; D009195:Peroxidase / Q000378:metabolism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000633:toxicity*; D017257:Ramipril / Q000031:analogs & derivatives* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D010972:Platelet Activating Factor; C052549:ramiprilat; D009195:Peroxidase; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D017257:Ramipril; D001920:Bradykinin