Effects of Kininase II Inhibitors on the Vasomotor Response to Bradykinin of Feline Intracranial and Extracranial Arteriesin vitroandin situ

Abstract

Bradykinin is known to effect a vasodilatation of feline cerebral arteries in situ and of both human and feline pial arteries in vitro. In order to demonstrate whether kininase II (localized within the vessel wall or in the surrounding tissue or fluid) influences the response to bradykinin, two different inhibitors of this bradykinin degradation enzyme were tested. Perivascular microapplication of potentiator C (10−10–10−4M) or captopril (10−10–10−3M) did not, by itself, change the diameter of feline pial arteries (87–305 μm) in situ. In a similar investigation, the dilating action of bradykinin (10−8–10−5M) was not modified by the simultaneous application of potentiator C or captopril (10−5M). Furthermore, the relaxing effect of bradykinin (10−10–10−4M) on isolated feline middle cerebral arteries (preconstricted with 5-hydroxytryptamine or prostaglandin F2α) was not influenced by the presence of captopril (10−7M). In contrast, when studied on isolated extracranial vessel segments (feline sublingual artery), bradykinin caused a concentration-dependent constriction of the artery. This constriction was completely reversed to dilatation in the presence of captopril (10−7M). Moreover, the characteristic effect of kininase II inhibition was demonstrated in the isolated guinea pig ileum preparation. In this instance, bradykinin induced a concentration-dependent contraction that was enhanced by potentiator C or captopril. We conclude, therefore, that bradykinin exerts variable responses on vascular smooth muscle, depending on the species used, the muscle location and experimental conditions. Finally, the in situ and in vitro findings for pial and middle cerebral arteries demonstrate that kininase II does not modify the dilating effect of bradykinin under our experimental conditions.