Comparative study of endotoxin‐induced hypotension in kininogen‐deficient rats with that in normal rats

Ueno, Akinori; Ishida, Hideki; Oh‐ishi, Sachiko

doi:10.1111/j.1476-5381.1995.tb13340.x

Cited by 23 publications

(12 citation statements)

References 36 publications

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“…interleukin-2) may also be inhibited by cyclic AMP phosphodiesterase inhibitors (Souness et al 1997). In addition, LPS is able to induce the release of endogenous factors such as platelet-activating factor (Doebber et al 1985;Szabo et al 1993b), bradykinin (Fleming et al 1992;Ueno et al 1995) or endothelin (Nakamura et al 1991), which can activate eNOS and then cause the release of NO from the endothelial cell and lead to the early fall in MAP. Here, our haemodynamic data show that TMP protects the early fall in MAP after administering rats with endotoxin, indicating that it may interfere with activation of the constitutive isoform of NOS in the endothelium which was activated by bradykinin, platelet-activating factor or endothelin and inhibited by the NOS inhibitor L-NAME (Szabo et al 1993a).…”

Section: Discussionmentioning

confidence: 98%

Tetramethylpyrazine prevents inducible NO synthase expression and improves survival in rodent models of endotoxic shock

Liao

Chen

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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This study is to investigate the possible mechanism of beneficial effects of tetramethylpyrazine (TMP) on endotoxic shock which we showed in our preliminary study (Liao et al. 1998; Proc Natl Sci Counc Repub China B 22:46-54). Here, we have confirmed the beneficial effects of TMP on the hypotension, vascular hyporeactivity to noradrenaline (NA), release of tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) in a rat model of circulatory shock induced by bacterial endotoxin (E. coli lipopolysaccharide, LPS). In addition, we further examined the expression of inducible NO synthase in the lung and in the aorta from these rats and evaluated the effect of TMP on the 36-h survival rate in a murine model of endotoxaemia. Male Wistar-Kyoto rats were anaesthetised and instrumented for the measurement of mean arterial pressure (MAP) and heart rate (HR). Injection of LPS (10 mg kg(-1), i.v.) resulted in an acute fall followed by a substantial fall in MAP within 4 h and an increase in HR. In contrast, animals pretreated with TMP (10 mg kg(-1), i.p.; at 30 min prior to LPS) maintained a significantly higher MAP but the tachycardia was further enhanced at 1-2 h when compared to rats given only LPS (LPS rats). The pressor effect of NA (1 microg kg(-1), i.v.) was also significantly reduced after the treatment of rats with LPS. Similarly, the thoracic aorta obtained from rats at 4 h after LPS showed a significant reduction in the contractile responses elicited by NA (1 microM). Pretreatment of LPS rats with TMP partially, but significantly, prevented this LPS-induced hyporeactivity to NA in vivo and ex vivo. The injection of LPS resulted in a bell-shaped change in plasma TNF-alpha level which reached a maximum at 1 h, whereas the effect of LPS on the plasma level of nitrate (an indicator of NO formation) was increased in a time-dependent manner. This increment of both TNF-alpha and nitrate levels was significantly reduced in LPS rats pretreated with TMP. Endotoxaemia for 4 h caused a significantly increased protein expression of iNOS in the lung and the aorta. In LPS rats pretreated with TMP, iNOS protein expression in lung and aorta homogenates was attenuated by 75+/-3% and 57+/-6%, respectively. In addition, the lack of evidence of pressor effect of TMP on rats with endotoxaemia for 4 h suggested that TMP inhibits the induction of iNOS rather than directly inhibiting NOS activity. Treatment of conscious ICR mice with a high dose of endotoxin (60 mg kg(-1), i.p.) resulted in a survival rate of only 15% at 36 h (n=20). However, therapeutic application of TMP (10 mg kg(-1), i.p.; at 0, 6, 15 and 24 h after LPS) increased the 36 h survival rate to 55% (n=20). Thus, TMP inhibits the expression of iNOS and mitigates the delayed circulatory failure caused by endotoxic shock in the rat. In addition, TMP also improves survival in a murine model of severe endotoxaemia.

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Section: Discussionmentioning

confidence: 98%

Tetramethylpyrazine prevents inducible NO synthase expression and improves survival in rodent models of endotoxic shock

Liao

Chen

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Lipopolysaccharide causes hypotension in normal rats, which is diminished by a B2R antagonist 60 . Furthermore, kininogen-deficient rats and mice lacking both B1R and B2R are resistant to LPS-induced septic shock.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, kininogen-deficient rats and mice lacking both B1R and B2R are resistant to LPS-induced septic shock. 25,60 Inducible NOS mRNA levels are increased by LPS in wildtype, but in mice lacking both B1R and B2R this increase is diminished. 25 Thus, bradykinin plays a role in the development of septic shock, in part by inducible NOS.…”

Section: Introductionmentioning

confidence: 99%

The kallikrein–kinin system in health and in diseases of the kidney

Kakoki

Smithies

2009

Kidney International

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Since kallikrein was discovered as a vasodilatory substance in human urine, the kallikrein–kinin system (KKS) has been considered to play a physiological role in controlling blood pressure. Gene targeting experiments in mice in which the KKS has been inactivated to varying degrees have, however, questioned this role, because basal blood pressures are not altered. Rather, these experiments have shown that the KKS has a different and important role in preventing changes associated with normal senescence in mice, and in reducing the nephropathy and accelerated senescence-associated phenotypes induced in mice by diabetes. Other experiments have shown that the KKS suppresses mitochondrial respiration, partly by nitric oxide and prostaglandins, and that this suppression may be a key to understanding how the KKS influences senescence-related diseases. Here we review the logical progression and experimental data leading to these conclusions, and discuss their relevance to human conditions.

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“…HK-deficient rats are protected from peptidoglycan-polysaccharide (PG-PS)-induced inflammatory arthritis as well as endototxin-induced hypotension (30,44). We, therefore, hypothesized that HK promotes inflammation.…”

Section: Discussionmentioning

confidence: 99%

High Molecular Weight Kininogen Activates B2 Receptor Signaling Pathway in Human Vascular Endothelial Cells

Kolte

Osman

Yang

et al. 2011

Journal of Biological Chemistry

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The nonenzymatic cofactor high molecular weight kininogen (HK) is a precursor of bradykinin (BK). The production of BK from HK by plasma kallikrein has been implicated in the pathogenesis of inflammation and vascular injury. However, the functional role of HK in the absence of prekallikrein (PK), the proenzyme of plasma kallikrein, on vascular endothelial cells is not fully defined. In addition, no clinical abnormality is seen in PKdeficient patients. Therefore, an investigation into the effect of HK, in the absence of PK, on human pulmonary artery endothe- The plasma kallikrein-kinin system (KKS) 2 consists of three proenzymes; factor XII (FXII, Hageman factor), prekallikrein (PK, Fletcher factor), and factor XI (FXI, plasma thromboplastin antecedent) as well as one cofactor; high molecular weight kininogen (HK, Fitzgerald factor). KKS is involved in the regulation of hemodynamics, inflammation, complement activation, angiogenesis, thrombosis, and fibrinolysis. Basically, all these proposed roles represent a range of overlapping effects that contribute to various extents toward vasodilation and healing. Therefore, the plasma KKS can be considered to have a spectrum of physiological effects, ranging at one extreme from a hemostatic state of vasodilation and promotion of smooth blood flow, all the way to a prothrombotic state. It is conceivable to suggest that other mechanisms proposed about respiratory, retinal, and renal systems can fit into this spectrum of physiological effects (1-3). There is accumulating evidence suggesting that when the plasma KKS is activated, the results are a sequential release of proteolytic enzymes and vasoactive peptides, generation of both angiogenic and anti-angiogenic molecules, stabilization of thrombus, and an increase in protease inhibitor activity in blood (4 -7). The activation of HK-PK complex on endothelial cells triggers vasodilation through smooth muscle relaxation, inhibits platelet aggregation, and induces proinflammatory responses. Of note, the direct assembly of HK, PK, and FXII on vascular smooth muscle cells (VSMC) also results in the activation of PK to kallikrein (8). The induction of these physiological reactions is caused by the release of the vasoactive peptide bradykinin (BK) from HK by kallikrein. Bradykinin B 2 receptor activation by BK mediates the activation of endothelial nitric-oxide synthase (eNOS) and phospholipase A 2 (PLA 2 ) leading to production of nitric oxide (NO) and prostacylin (PGI 2 ). Evidence suggests that BK phosphorylates p44/42 mitogen-activated protein kinase in VMSC, which is blocked by BK antagonist HOE-140 (8).Besides having a direct effect on blood vessels, the HK-PK complex has also been shown to mediate the effects of other pro-inflammatory molecules. Recent study suggests that the inhibitors of both BK and factor XII activity protect from mast cell-induced effects not only in patients but also in genetically engineered mouse models. The authors proposed that this class of inhibitors could be useful to treat allergic diseases (9)....

show abstract

Comparative study of endotoxin‐induced hypotension in kininogen‐deficient rats with that in normal rats

Cited by 23 publications

References 36 publications

Tetramethylpyrazine prevents inducible NO synthase expression and improves survival in rodent models of endotoxic shock

Tetramethylpyrazine prevents inducible NO synthase expression and improves survival in rodent models of endotoxic shock

The kallikrein–kinin system in health and in diseases of the kidney

High Molecular Weight Kininogen Activates B2 Receptor Signaling Pathway in Human Vascular Endothelial Cells

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