Which is the Effective Agent — Bradykinin or Prostaglandins — on the Isolated Mammalian Heart
It is well known that bradykinin in minute doses increases perfusion flow and the height of the beats of the isolated mammalian heart (1). In Reston, Va., last October, the question was raised whether the effects of bradykinin (Bk) on the isolated mammalian heart perfused by the Langendorff technique, could be due to a release of prostaglandin (PGE2), since the latter was able to produce a similar effect on the coronary perfusion flow and on the force of contraction. Such an indirect effect of Bk mediated by PGE2 could be reasonable owing to the many reports establishing that Bk is able to stimulate synthesis of prostaglandins (2). On the other hand PGE, has been found to potentiate the effects of Bk in pain production (3), swelling of the rat’s paw (4), increase in vascular permeability (5) and in the so-called pseudo-affective reaction to Bk when injected into the splenic artery (6). In a series of experiments on the isolated guinea pig heart (Langendorff’s technique) the effects of Bk and PGE were compared and the results obtained fully demonstrated the impossibility of explaining by synthesis or release of PGE2 the immediate effect of minute doses (0.001 to 0.01 μg) of Bk on the perfusion flow and height of contraction. In our experiments, PGE2 acts in a quite different way in higher (0.1 to 1.0 μg) closes inducing an immediate reduction in the height of contraction and a rather delayed effect on the perfusion flow accompanied by sustained increase in height of contraction. The opposite possibility, namely that prostaglandin (PGE2) may act by release of an endogenous mediator is more likely to explain the delayed effect on coronary flow and height of contraction. A release of catecholamines by PGE2 has been considered but excluded, since a β-sympatholytic agent (Inderal) which blocks the effect of epinephrine, did rather enhance (potentiate) the secondary effect of PGE2. The alternative possibility of formation of Bk from endogenous sources of bradykininogen was considered as a likely by the fact that a bradykinin potentiating factor (BPF) definitely enhanced the secondary effects of PGE2. Furthermore, Inderal which potentiated the secondary effect of PGE2 also increased the primary effect of Bk alone or associated with BPF. If confirmed, the possibility that prostaglandins may release Bk from its precursor in tissue, would be a first instance in which prostaglandin may constitute a Bk-forming agent, that could explain part of the potentiating action of PGE, on several effects of Bk, as mentioned above. These results await further confirmation by experiments currently being carried out in our laboratory.
KeywordsVascular Permeability Secondary Effect Coronary Flow Splenic Artery Alternative Possibility
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