Evidence for a possible role of the brain kallikrein-kinin system in the modulation of the cerebral circulation.

Kamitani, Toshiharu; Little, Marcia H.; Ellis, Elliot F.

doi:10.1161/01.res.57.4.545

Cited by 47 publications

(8 citation statements)

References 40 publications

(34 reference statements)

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“…However, the EDRF for calcium ionophore in brain microvessels may be identical to that for bradykinin, another agent of potential pathophysiologic importance. 25 The EDRF for bradykinin is also cyclooxygenase dependent. 25 The diameter changes we observed averaged 7-11% for calcium ionophore and ACh.…”

Section: Discussionmentioning

confidence: 99%

Calcium ionophore and acetylcholine dilate arterioles on the mouse brain by different mechanisms.

Rosenblum

McDonald

Wormley

1989

Stroke

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Pial arterioles on the surface of the mouse brain were observed in vivo under a chamber with a glass window. When placed under the window, calcium ionophore, acetylcholine, and previously acidified sodium nitrite each dilated the arterioles. If the cyclooxygenase inhibitors indomethacin or acetylsalicylic acid were first placed in the chamber, subsequent dilation of the arterioles by calcium ionophore was reduced to essentially zero. Similar blockade of cyclooxygenase failed to significantly reduce dilation by acetylcholine or sodium nitrite. We have previously shown that dilations by calcium ionophore and acetylcholine were endothelium dependent. Our present experiments show that the endothelium-dependent mechanism for dilation by calcium ionophore is cyclooxygenase dependent, while that for acetylcholine is not. This implies that, in pial arterioles, the endothelium-derived relaxing factor for acetylcholine differs from that for calcium ionophore. This agrees with data from other microvascular beds. I n mouse and cat cerebral microvessels on the surface of the brain (pial arterioles), we have demonstrated endothelium-dependent relaxation and constriction in vivo.1 -3 Instead of directly relaxing vascular smooth muscle, some (but not all) dilators relax these arterioles by causing their endothelium to release a relaxing mediator. The dilators for which we have shown this phenomenon are calcium ionophore A-23187, acetylcholine (ACh), and bradykinin. These same dilators have been shown by others to produce endothelium-dependent relaxation of large conductance vessels in vitro. 4 -5 In conductance arteries, there is evidence that the endothelium-derived relaxing factor (EDRF) is the same for all three dilators. 6 Moreover, this EDRF (sometimes called classical EDRF) is not cyclooxygenase dependent and hence relaxation by the three dilators is not blocked by cyclooxygenase inhibitors such as indomethacin.1 -4 However, in large vessels, prostacyclin (a product of cyclooxygenase activity) is also recognized as an EDRF, albeit not the classical EDRF. Moreover, there may be other EDRFs released from other large vessels.

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Section: Discussionmentioning

confidence: 99%

Calcium ionophore and acetylcholine dilate arterioles on the mouse brain by different mechanisms.

Rosenblum

McDonald

Wormley

1989

Stroke

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“…- 25 In cats and mice, bradykinin-induced cerebral vasodilatation appears to be mediated by generation of oxygen radicals. 1 -2 Our preliminary study showed that bradykinin-induced cerebral vasodilatation in rats was almost completely inhibited by catalase.…”

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confidence: 99%

Endothelium-dependent responses of cerebral blood vessels during chronic hypertension.

et al. 1991

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Acetylcholine produces less dilatation of pial arterioles in stroke-prone spontaneously hypertensive rats (SHRSP) than in normotensive (WKY) rats. Responses of cerebral vessels to acetylcholine and bradykinin appear to involve different mechanisms. Our first goal was to determine whether responses of pial arterioles to bradykinin are impaired in SHRSP. Diameter of pial arterioles (20-60 /tm) was measured using intravital microscopy in WKY rats and SHRSP (

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“…At least two mechanisms could be involved: (i) a depletion of local tissue kininogen stores, or (ii) occupation of neural receptor sites by continuously formed endogenous kinins. A depletion of brain kininogen has been implicated in the desensitization of rabbit pial arterioles to the second dose of kallikrein, since the arterioles still responded normally to exogenous bradykinin (Kamitani, Little & Ellis, 1985). In the present experiments, tachyphylaxis to kallikrein was associated with a long-lasting (up to 60 min) reduction of reflexogenic effects of exogenous kinins, but not that of capsaicin which also involves activation of cardiac afferents incorporated in spinal thoracic sympathetic nerves (StaszewskaWoolley et al 1986).…”

Section: Effects Of Epicardial Treatment By Aprotininmentioning

confidence: 45%

Participation of the kallikrein‐kinin‐receptor system in reflexes arising from neural afferents in the dog epicardium.

Staszewska-Woolley

Woolley

1989

The Journal of Physiology

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SUMMARY1. Reflexogenic effects of bradykinin, lysyl-bradykinin and endogenously formed kinins on neural afferents of the left ventricular epicardium were studied in anaesthetized, open-chest dogs.2. Epicardial application of either bradykinin (001-10 tg), lysyl-bradykinin (001-1O jug) or tissue kallikrein (0003-1 U) consistently resulted in dose-related increases in blood pressure and heart rate. The pressor and heart rate responses to epicardial kallikrein were slower in onset and longer lasting than those evoked by bradykinin or lysyl-bradykinin. The effects of kallikrein, but not those of exogenous kinins, were subject to tachyphylaxis. The application of higher doses of kallikrein (0 1 or 1 U) also resulted in long-lasting desensitization of the epicardium to the effects of bradykinin.3. Treatment of the epicardium with a proteinase inhibitor, aprotinin, prevented the reflexogenic effects of kallikrein but not those of bradykinin or lysyl-bradykinin. Treatment with aprotinin also counteracted post-kallikrein desensitization of sensory receptors of the ventricular epicardium to the reflexogenic effect of bradykinin.4. Superfusion of the epicardium with a selective B2 receptor antagonist, D-Arg[Hyp3,Thi5 8,D-Phe7]-bradykinin, was equally effective in antagonizing the reflexogenic effects of kallikrein, bradykinin and lysyl-bradykinin.5. We conclude that the response to epicardial application of kallikrein indicates an ample presence of endogenous substrate for local formation of bradykinin and/or related kinins. These then initiate reflex activation of the cardiovascular system by interacting with specific B2 receptors associated with sympathetic afferent neurones in the dog epicardium. We suggest that the kallikrein-kinin-receptor system has a role in the reflex functioA of the cardiac sympathetic afferents in both physiological and pathological conditions.

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Evidence for a possible role of the brain kallikrein-kinin system in the modulation of the cerebral circulation.

Cited by 47 publications

References 40 publications

Calcium ionophore and acetylcholine dilate arterioles on the mouse brain by different mechanisms.

Calcium ionophore and acetylcholine dilate arterioles on the mouse brain by different mechanisms.

Endothelium-dependent responses of cerebral blood vessels during chronic hypertension.

Participation of the kallikrein‐kinin‐receptor system in reflexes arising from neural afferents in the dog epicardium.

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