Kinins induce abnormal vascular reactivity

Abstract

Previous studies have shown that after experimental neural trauma or acute hypertension the brain produces superoxide anion radicals, and brain arterioles display endothelial lesions, dilation, and loss of normal reactivity in response to a decrease in CO2 tension. Because these abnormalities are prevented by pretreatment with free radical scavengers or inhibitors of the cyclooxygenase component of prostaglandin (PG) H synthase, arachidonic acid metabolism by PGH synthase with concomitant formation of tissue injuring oxygen radicals causes the vascular damage. The purpose of the present experiments was to determine whether kinins, which are known to stimulate arachidonate metabolism and to induce cerebral arteriolar dilation via production of superoxide anion, may be involved in initiating the cerebrovascular abnormalities produced by neural trauma in cats. The diameter and reactivity of untreated in vivo pial arterioles on one cerebral cortex was compared with the diameter and reactivity of pial arterioles on the contralateral cortex, which were pretreated topically with a competitive receptor antagonist, which is specific for kinins. Before fluid percussion neural trauma was induced, arterioles on both cerebral hemispheres constricted normally to a decrease in CO2 tension. After injury, the arterioles on the untreated cortex dilated and did not constrict in response to a decrease in arterial CO2 tension, whereas the arterioles pretreated with the kinin antagonist dilated less and displayed normal reactivity to CO2. These experiments demonstrate that a specific kinin receptor stimulates PGH synthase-dependent, free radical-mediated cerebrovascular injury. Given the ubiquitous distribution of the kallikrein-kinin system, we propose that kinins may be an important common mediator of systemic vascular injury and abnormal vascular reactivity.

Development of hyperthermia following intracerebroventricular administration of endotoxin in the rat: effect of kinin B1 and B2 receptor antagonists

“…In addition, autoradiographic studies have identified specific bradykinin binding sites in the brain and spinal cord (Fujiwara et al, 1989;Privitera et al, 1992). Kinin formation and activity has been demonstrated during different forms of CNS trauma, including brain lesion injury and cerebral ischaemia (Maier-Hauff et al, 1984;Unterberg et al, 1986;Ellis et al, 1987Ellis et al, , 1988Kamiya et al, 1990Kamiya et al, , 1993Wahl et al, 1993).…”

Bradykinin Induces Interleukin‐6 Expression in Astrocytes Through Activation of Nuclear Factor‐κB

“…The components of the kinin‐kallikrein system are also expressed in brain (Walker et al, 1995). In the brain, elevated extracellular levels of bradykinin are found in cerebral trauma and ischemia (Ellis et al, 1988 ; Kamiya et al, 1993). As in peripheral tissue, bradykinin can increase the permeability of brain capillaries (Wahl et al., 1988).…”

“…As in peripheral tissue, bradykinin can increase the permeability of brain capillaries (Wahl et al., 1988). This effect of bradykinin has been exploited to open the blood‐brain barrier for chemotherapy in brain tumors (Matsukado et al, 1996), but may also underlie the vasogenic brain edema found in cerebral ischemia (Kamiya et al, 1993 ; Relton et al, 1997) and trauma (Ellis et al, 1988).…”

Kininogen and Kinin in Experimental Spinal Cord Injury

“…Recently, the kallikrein-kinin system has been implicated in posttraumatic vascular injury of the CNS (Ellis et al, 1987(Ellis et al, , 1988(Ellis et al, , 1989 and in vasogenic brain edema (Maier-Hauff et al, 1984;Unterberg and Baethmann, 1984;Unterberg et al, 1986). Recently, the kallikrein-kinin system has been implicated in posttraumatic vascular injury of the CNS (Ellis et al, 1987(Ellis et al, , 1988(Ellis et al, , 1989 and in vasogenic brain edema (Maier-Hauff et al, 1984;Unterberg and Baethmann, 1984;Unterberg et al, 1986).…”

“…Vascular injury plays an important role in traumatic damage of the CNS. Recently, the kallikrein-kinin system has been implicated in posttraumatic vascular injury of the CNS (Ellis et al, 1987(Ellis et al, , 1988(Ellis et al, , 1989 and in vasogenic brain edema (Maier-Hauff et al, 1984;Unterberg and Baethmann, 1984; Unterberg et al, 1986). Vasoactive kinins, including bradykinin and Tkinin, among others, are released from their macromolecular kininogen precursors by proteolytic enzymes, the tissue or T-kininogenase kallikreins (Muller-Ester1 et al, 1986).…”