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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both under physiologic conditions and after short-term ischemia (1-3 min) kallikrein and locally synthesized prostaglandins contribute to control renal blood flow. In the present experiment the antiproteases aprotinin and gabexate-mesilate were administered to rabbits in an attempt to show whether the hemodynamic changes produced by 60 min of normothermic ischemia, i.e., postischemic hyperemia and reduction of vascular resistance, were equally mediated by kallikrein. Vascular responses were evaluated by determining renal cortical blood flow using radioactively labelled microspheres, by calculating vascular resistances, and by measuring the diameters of renal medullary vessles. Kidneys exposed to normothermic ischemia and sham-operated control organs of animals treated with aprotinin (2 X 40,000 KIU/kg body weight) and gabexate-mesilate (2 X 7 mg/kg body weight) were compared with those of rabbits which were analogously operated, but did not receive any drugs. As the antiproteases used did not significantly affect the hyperemia and the reduction of renal cortical vascular resistance seen after 60 min of normothermic ischemia, these phenomena are apparently not mediated by kallikrein. Renal medullary vasodilatation (arteriolae rectae) was significantly lower under aprotinin than in untreated ischemic kidneys, and was not longer demonstrable in gabexate-mesilate-treated animals. Thus, the effect of gabexate-mesilate was superior to that of aprotinin. Whether the antiprotease action is due to an unspecific membrane-stabilizing, to a general enzyme-inhibiting, or to a specific kallikrein-inhibiting effect, is still unclear.
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PMID:Effects of antiproteases (aprotinin and gabexate-mesilate) on the postischemic vascular response of the kidney. 619 20

In spite of numerous work done in this field it is not clarified so far how the acceleration of the capillary blood flow, of glucose uptake, and of muscle growth occurring during work and after ischemia is controlled in muscle tissue. Since the signal for the induction of these responses stems from inside the cell, tissue factors have been postulated which should be responsible for the enlargement of the capillary net and the improvement of the tissue's insulin sensitivity. The accumulation of new evidences during the last few years points to an involvement of the kallikrein-kinin-prostaglandin system.
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PMID:The kallikrein-kinin-prostaglandin system: involvement in the control of capillary blood flow and substrate metabolism in skeletal muscle tissue. 634 76

Vasogenic edema was induced in mongrel cats by cold injury to study uptake and activation of the plasma-kallikrein-kinin system in central nervous system (CNS) tissue. A method was developed for quantitative assessment of kinin formation in affected brain tissue areas. Gross disruption of the blood-brain barrier by focal trauma causes marked penetration of plasma kininogens into necrotic and edematous brain tissue. Moreover, the kallikrein-kinin (KK) system was activated in both necrotic and perifocal edematous areas, and was markedly enhanced by additional cerebral ischemia. Formation of kinins in necrotic brain tissue led to consumption of approximately 60% to 80% of the amount of kininogens being taken up. In perifocal edematous tissue, formation of kinins was less pronounced, or even absent. However, if cerebral ischemia evolved after severe intracranial hypertension, kinins were also formed in the perifocal edematous brain. The intravascular origin of kininogens found in pathological tissue areas secondary to injury was deduced from the observation that cerebral tissue of the contralateral hemisphere with an intact blood-brain barrier had no measurable quantities of kininogens. Consumption of plasma kininogens or formation of kinins were assessed as the difference of the total amount of plasma kininogens taken up into the tissue minus the amount of kininogens found in the brain at postmortem examination. The data indicate that uptake and activation of the plasma-KK system might occur under all pathological conditions in which blood-brain barrier damage permits cerebral penetration of plasma proteins, such as with cerebral contusion, focal ischemia, and tumors. The potent pathophysiological mechanisms induced by kinins in CNS tissue, such as formation of brain edema, microcirculatory dysfunction, and enhancement of blood-brain barrier permeability, together with their formation in focal and perifocal pathological brain tissue, provide further support for a mediator function of the KK system. Methods that specifically interfere with the formation of kinins in damaged brain should therefore be expected to attenuate vasogenic edema.
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PMID:The kallikrein-kinin system as mediator in vasogenic brain edema. Part 2: Studies on kinin formation in focal and perifocal brain tissue. 656 63

It has been reported that kinins mediate part of the beneficial cardiac effects induced by treatment with angiotensin-converting enzyme inhibitors in situations such as ischemia-reperfusion injury, myocardial infarction, and cardiac hypertrophy. However, it is not known whether the heart contains an independent kallikrein-kinin system. We measured kallikrein in tissue and in the incubation medium of heart slices. Heart slices released active and total (trypsin-activatable) kallikrein into the medium (46 +/- 5 and 380 +/- 18 pg bradykinin/mg, respectively, after 1 hour and 78 +/- 6 and 654 +/- 14 pg bradykinin/mg after 2 hours, n = 7). Release was not due to tissue damage because lactate dehydrogenase, a cytosolic marker, decreased from 8.9 +/- 2.9 to 2.9 +/- 1.0 U/mg per hour. Although kallikrein was released, total tissue kallikrein in the slices did not change (423 +/- 25 pg bradykinin/mg in nonincubated slices and 370 +/- 42 pg bradykinin/mg after 2 hours, P = NS), suggesting pool replenishment. Cardiac kallikrein activity was inhibited by incubation with anti-glandular kallikrein antibodies. Pretreatment with the protein synthesis inhibitor puromycin (10 mg IP) lowered release of active kallikrein from 78 +/- 6 to 22 +/- 4 pg bradykinin/mg and total kallikrein from 654 +/- 14 to 113 +/- 9 pg bradykinin/mg (P < .001). By using reverse transcription polymerase chain reaction with kallikrein family oligonucleotide primers and a specific kallikrein probe, we found that mRNA for tissue kallikrein is present in both atrial and ventricular RNA. Kallikrein activity was also detected in primary cultures of neonatal rat atrial and ventricular cardiocytes and their incubation medium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A local kallikrein-kinin system is present in rat hearts. 820 28

It was found that clinical symptoms of the III degree ischemia were not reliable criteria of reversibility of ischemic disorders which requires additional information. The express-histochemical method of examination of bioptates of the ischemic extremity muscles is thought to be highly informative under such conditions as well as studying indices of the prekallikrein-kallikrein system of blood. The leading importance may be attached to the factor of time of severe ischemia when no additional information can be obtained. In patients with the III degree ischemia and its duration over 12 hours primary amputation of the extremity is indicated without an attempt being made to reestablish the blood flow.
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PMID:[The time of severe acute ischemia as a risk factor in the restoration of the circulation in the ischemic extremity in embolisms of the major arteries]. 859 14

Growing evidence points to the existence of the components of the kallikrein-kinin-system (KKS) in cardiac and vascular tissue forming systemic and local KKS pathways involving different cell types like endothelial cells, cardiomyocytes and vascular smooth muscle cells. Kinins may contribute to the regulation of the cardiovascular system in health and disease and to the pharmacological effects of cardiovascular agents via autocrine-paracrine mechanisms. Based on observations from experimental models of hypertension, hypertrophy, ischemia, remodelling and preconditioning one can assume that modulation of local KKS pathways is instrumental for endogenous cardio- and vasculoprotective mechanisms. The role of kinins as possible mediators of such protective mechanisms is not only based on the existence of their generating pathways and their release, but also on observations that kinins, when given locally or being increased by inhibition of their breakdown, exert beneficial cardiovascular effects, whereas antagonism of their receptors worsens these effects. Indispensable pharmacological tools like ACE inhibitors and kinin receptor antagonists have helped to clarify these assumptions, which are now further elucidated by molecular biology and by clinical research. Especially the wealth of experimental and clinical findings with ACE inhibitors present a continuous challenge to investigate the role of kinins in the cardiovascular system and to have a closer look at the interdependence of KKS and the Renin-Angiotensin-System (RAS). Within our decade one might not only reach a clearer molecular perception of kinins in the cardiovascular system, and their role in human health and disease, but might also come to improved innovative treatment by modulation of the KKS pathways.
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PMID:Kinins in the cardiovascular system. 885 52

All components of an intracerebral kallikrein-kinin system have been described. Thus, bradykinin (BK) acting from the parenchymal site as well as from the blood site may influence cerebral microcirculation. BK is a potent dilator of extra- and intraparenchymal cerebral arteries when acting from the perivascular site. The vasomotor effect of BK is mediated by B2 receptors which appear to be located at the abluminal membrane of the endothelial cell. The effect of BK is mediated by NO. prostanoids, free radicals, H2O2 or leukotrienes depending on the animal species and on the location of the artery. Selective opening of the blood-brain barrier for small tracers (Na(+)-fluorescein; MW, 376) has been found in cats during cortical superfusion or intraarterial application of BK. This leakage is mediated by B2 receptors located at the luminal and abluminal membrane of the endothelial cells. Formation of brain edema has been found after ventriculo-cisternal perfusion or interstitial infusion of BK. This can be explained by increase of vascular permeability and cerebral blood flow due to arterial dilation thus enhancing driving forces for the extravasation. An increase of the BK concentration in the interstitial space of the brain up to concentrations which induce extravasation, dilatation and oedema formation has been found under several pathological conditions. Thus, BK may be involved in oedema formation after cold lesion, concussive brain injury, traumatic spinal cord and ischemic brain injury. The mediator role of BK in brain edema is further supported by therapeutic results. Brain swelling due to cold lesion or ischemia could be diminished by treatment with kallikrein-inhibitors. Similarly, dilatation of cerebral arterioles after concussive brain injury was reduced by blockade of B2 receptors. Thus, all criteria favour BK as one mediator of vasogenic oedema.
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PMID:Vasomotor and permeability effects of bradykinin in the cerebral microcirculation. 885 59

Ischemic diseases of heart and brain are the primary causes of mortality in industrialized nations. The ischemic injury with the consecutive reperfusion is responsible for the disturbance of microcirculation with ensuing tissue damage and organ dysfunction. Recent evidence suggests that oxygen-derived free radicals and activated polymorphonuclear leukocytes produced in ischemic tissue are instrumental in the development of ischemic cell injury. In pancreas, ischemia/ reperfusion is proposed as a potentially damaging factor accounting in part for the pathogenesis of acute pancreatitis. Apart from ischemia/reperfusion injury, the kallikrein-kinin system mediates acute inflammation associated with enhanced capillary permeability and accumulation of polymorphonuclear leukocytes, cardinal features of ischemia/reperfusion injury also in acute pancreatitis. Therefore, it seems reasonable to use bradykinin-antagonists to influence postischemic reperfusion injury of the pancreas. In the following, we describe the pathophysiology of ischemia/reperfusion injury with special reference to the pancreatic microcirculation and morphological changes as observed in a model of complete and reversible ischemia. Furthermore, we will discuss the effects of two bradykinin-antagonists (HOE 140 and CP-0597) on functional integrity of the pancreas after ischemia/ reperfusion.
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PMID:Ischemia and reperfusion in pancreas. 922 Apr 31

There is growing evidence for a local kallikrein-kinin system in the heart. In the ischemic heart the enhanced generation and release of kinins seem to have cardioprotective actions. In isolated rat hearts with ischemia-reperfusion injuries, perfusion with bradykinin reduces the duration and incidence of ventricular fibrillations, improves cardiodynamics, reduces release of cytosolic enzymes, and preserves energy-rich phosphates and glycogen stores. In anesthetized animals, intracoronary infusion of bradykinin is followed by comparable beneficial changes and limits infarct size. Inhibition of breakdown of bradykinin and related peptides induces similar beneficial cardiac effects. Treatment with angiotensin-converting enzyme (ACE) inhibitors such as ramipril increases cardiac kinins and reduces postischemic reperfusion injuries in isolated rat hearts as well as infarct size and remodeling in postinfarcted animals, respectively. Blockade of B2 kinin receptors increases ischemia-induced effects. In isolated hearts, ischemia-reperfusion injuries intensify with the B2 kinin receptor antagonist icatibant, which also abolishes the cardioprotective effects of ACE inhibitors and of exogenous bradykinin. Infarct size reduction by ACE inhibitors and bradykinin in anesthetized animals is reversed by icatibant. Kinins contribute to the cardioprotective effects associated with ischemic preconditioning. Preconditioning or bradykinin-induced antiarrhythmic and infarct size-limiting effects are attenuated by icatibant.
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PMID:Beneficial effects of bradykinin on myocardial energy metabolism and infarct size. 929 64

Kinins acting on the B2 receptor appear to be involved in the cardioprotective effect of preconditioning on myocardial ischemia/reperfusion injury. We tested the hypothesis that in mice lacking the gene encoding for the B2 kinin receptor (B2 knockout mice; B2-KO) as well as in rats deficient in high-molecular-weight (HMW) kininogen (Brown Norway Katholiek rats; BNK), the cardioprotective effect of preconditioning is diminished or abolished. 129SvEvTac (SV129) mice and Brown Norway rats (BN) served as controls. We confirmed that plasma HMW kininogen in BNK rats was 100-fold lower than in BN and 140-fold lower than in Sprague-Dawley rats (33+/-4 versus 1814+/-253 and 2397+/-302 ng/mL, P<.01). Each strain of mice was divided into (1) controls (without preconditioning); (2) one cycle of preconditioning (3 minutes ligation and 5 minutes reperfusion); and (3) three cycles of preconditioning. Each strain of rats was divided into (1) controls; and (2) three cycles of preconditioning. All animals were subjected to 30 minutes of ischemia and 120 minutes of reperfusion. In SV129 controls, the ratio of infarct size to risk area (IS/AR) was 55.6+/-4.6%. One and three cycles of preconditioning reduced IS/AR to 38.6+/-3.2% and 31.1+/-2.3%, respectively (P<.05 and P<.01 versus control). This protective effect was absent in B2-KO mice: IS/AR was 54.8+/-2.9% in controls, 58.5+/-3.6% with one cycle of preconditioning, and 58.5+/-3.4% with three cycles. In BN rats without preconditioning, IS/AR was 84.7+/-3.9%; preconditioning reduced it to 61.6+/-3.4% (P<.01). In BNK rats, IS/AR was 87.1+/-4.8% in controls and 84.3+/-4.1% with preconditioning. Preconditioning also prevented reperfusion arrhythmias in BN but not BNK rats. Within species, risk area, mean blood pressure, and heart rate were similar between strains. We concluded that (1) preconditioning protects the heart against ischemia/reperfusion injury in mice and rats; (2) activation of prekallikrein, which in turn generates kinins from HMW kininogen, may contribute to the effect of preconditioning; and (3) an intact kallikrein-kinin system is necessary for the cardioprotective effect of preconditioning.
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PMID:Role of kinins in the cardioprotective effect of preconditioning: study of myocardial ischemia/reperfusion injury in B2 kinin receptor knockout mice and kininogen-deficient rats. 932 15


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