Abstract
Bradykinin (BK) plays an important role in different physiological processes including the general preservation and modulation of vascular systems. The present study was designed in order to examine the effect of BK on isolated rat femoral artery rings and to investigate the participation of intact endothelium, cyclooxygenase products, Ca2+ channels, Na+/K+–ATPase, and B2 kinin receptors in BK-induced action. Circular artery segments were placed in organ baths. The endothelium was mechanically removed from some arteries. Concentration–contraction curves for BK were obtained in the rings previously equilibrated at the basal tone. BK produced a concentration–dependent contraction, which was reduced by endothelial denudation. The BK–induced effect was almost completely inhibited by indomethacin (cyclooxygenase inhibitor) or OKY–046 (thromboxane A2–synthase inhibitor). Nifedipine (Ca2+ channel blocker), ouabain (Na+/K+–ATPase inhibitor), or HOE–140 (selective B2 kinin receptor antagonist) significantly reduced the BK–evoked effect. In conclusion, it can be proposed that BK produces concentration– and endothelium–dependent contractions of the isolated rat femoral artery, which is for the most part a consequence of B2 kinin receptor activation. Cyclooxygenase contractile products, especially thromboxane A2, play a significant role in this course of action. The transduction mechanism involved in the process of BK–induced femoral artery contraction include the activation of voltage–gated Ca2+ channels, and in a smaller extent Na+/K+–ATPase as well.
Highlights
Bradykinin is an endogenous polypeptide, which belongs to the kinin family
Considering the obtained pEC50 values, bradykinin produced notably more potent contractions in male rats, which was on the other hand equi-effective, if merely maximal contractile responses were compared (Table 1, Figure 1A-B)
Taking into account that there was an obvious influence from gender involved in the vascular response to bradykinin, and in order to reduce the number of animals required for our investigation, the further experiments included only rings obtained from the male animals, which was in full accordance with the “The 3Rs” principle [16,17,18]
Summary
Bradykinin is an endogenous polypeptide, which belongs to the kinin family. It controls and modulates important physiological processes and has been recognized as an exceptionally useful pharmacological tool. With consideration of vascular system effects, bradykinin can produce vasoconstriction by the activation of B2 kinin receptors located on smooth muscle cells, and oppositely vasodilatation after the activation of B1 and endothelial B2 kinin receptors. This has been shown to be largely dependent upon the investigated species or/and the chosen blood vessel [8, 12, 13]. Taking the previous considerations into account, followed by the known fact that the femoral artery represents an important target site connected to various pathological conditions, and that the bradykinin action on this blood vessel is still under investigation, the present isolated organ bath study was undertaken in the following order: (1) to examine the effect of bradykinin on isolated rat femoral artery rings, (2) to investigate the possible participation of intact endothelium in bradykinin-evoked action, (3) to define a possible role of cyclooxygenase products in bradykinin action on the investigated blood vessel, (4) to establish if voltage-gated Ca2+ channels and Na+/K+-ATPase are important for the transduction mechanism related to the bradykinin vascular effect; (5) and to determine if B2 kinin receptors are involved in bradykinin’s action on the rat femoral artery
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