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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to investigate the role of bradykinin as well as that of platelet-activating factor in the endotoxin-induced acute vascular permeability increase in the dorsal skin of rats by use of kininogen-deficient and normal Brown-Norway rats. In the kininogen-deficient rats, the dose-dependent dye exudation induced by endotoxin was about one half of that in the normal rats at any doses of endotoxin tested (0.1-1.0 mg per site), whereas the dose-response curves obtained by bradykinin (1-100 nmol per site), platelet-activating factor (0.1-1 nmol per site) or histamine (50-500 nmol per site) were the same in both rats. This effect induced by endotoxin in the kininogen-deficient rats was not changed by pretreatment with a bradykinin B2 receptor antagonist, HOE140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin, 1 mg kg-1 i.v.), whereas the endotoxin-induced response in the normal rats was attenuated by the receptor antagonist. These responses in both kininogen-deficient and normal rats were significantly inhibited by a selective platelet-activating factor antagonist, TCV309 (3-bromo-5-[N-phenyl-N-[2-[[2-(1,2,3,4,-tetrahydro-2- isoquinolylcarbonyl-oxy)-ethyl]-carbamoyl]-ethyl]carbamoyl]-1-prop yl- pyridinium nitrate, 0.1 mg kg-1 i.v.). These results suggest that bradykinin could be one of the major mediators in the endotoxin-induced vascular permeability increase in rat skin in addition to platelet-activating factor.
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PMID:Involvement of bradykinin in endotoxin-induced vascular permeability increase in the skin of rats. 854 29

In 1979, we found a strain of kininogen-deficient Brown Norway rats. Since then, several studies have used these animals as negative controls of the involvement of the kinin system in physiological and pathophysiological processes. The cause of this deficiency has now been elucidated. This article reviews studies performed with these kininogen-deficient rats. These investigations have mainly focused on the links between the kinin system and the kidneys, hypertension, salivary glands, acute inflammatory reactions, cysteine proteinase inhibition, lymphatic tissues, coagulation, and cardiovascular shock states.
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PMID:The brown Norway rats and the kinin system. 884 78

A hypotensive response to intravenously injected des-Arg9-bradykinin was elicited in young male Brown Norway rats (8-12 weeks-old), when the rats were intravenously injected with endotoxin (30 micrograms/kg) 24 h before they were repeatedly injected with bradykinin or des-Arg9-bradykinin. The potency of this inducible dose-dependent hypotensive response to des-Arg9-bradykinin was comparable to that induced by bradykinin on a molar base (3-30 nmol/kg). A hypotensive response to des-Arg9-bradykinin could also be induced when the rats were pretreated with endotoxin 6 h before. However, the potency of the response was less than that induced by 24-h pretreatment. This inducible response to des-Arg9-bradykinin did not occur in old rats (8-10 months old). Intravenous infusion of a B1-receptor antagonist, des-Arg9-[Leu8]-bradykinin, suppressed the hypotensive response of des-Arg9-bradykinin. These results suggest that the B1-receptor, mediating hypotension in rats, was inducible through time-dependent and age-dependent sensitization by endotoxin pretreatment.
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PMID:Induction of a B1-receptor mediating hypotensive response in young brown Norway rats. 885 24

Renal kallikrein is one of the tissue kallikreins, and the distal nephron is fully equipped as an element of the kallikrein-kinin system. Although a low excretion of urinary kallikrein has been reported in essential hypertension, the results from studies on patients with hypertension are not consistent. Congenitally hypertensive animals also excrete lowered levels of urinary kallikrein, but the effects of this are yet unknown. Extensive genetic and environmental studies on large Utah pedigrees suggest that the causes of hypertension are closely related to the combination of low kallikrein excretion and the potassium intake. Mutant kininogen-deficient Brown Norway-Katholiek rats, which cannot generate kinin in the urine, are very sensitive to salt loading and to sodium retention by aldosterone released by a non-pressor dose of angiotensin II, which results in hypertension. The major function of renal kallikrein-kinin system is to excrete sodium and water when excess sodium is present in the body. Failure of this function causes accumulation of sodium in the cerebrospinal fluid and erythrocytes, and probably in the vascular smooth muscle, which become sensitive to vasoconstrictors. We hypothesize that impaired function of the renal kallikrein-kinin system may play a pivotal role in the early development of hypertension. Inhibitors of kinin degradation in renal tubules and agents, which accelerate the secretion of urinary kallikrein from the connecting tubules and increase the generation of urinary kinin, may be novel drugs against hypertension.
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PMID:Pivotal role of renal kallikrein-kinin system in the development of hypertension and approaches to new drugs based on this relationship. 886 49

The influence of some peptidase inhibitors on oedema and plasma extravasation induced by bradykinin and carrageenan in rat paw was evaluate. Bradykinin-induced oedema in normal rats was increased by o-phenanthroline (3.10(-2) M), by captopril (10(-6) M to 10(-4) M), by lisinopril (10(-6) M to 10(-4), or by lisinopril (10(-5) M) in combination with apstatin (8.10(-5) M or 1.4 10(-4) M). It was not modified by phosphoramidon (10(-6) M to 10(-5) M) and by diprotin A (10(-3) M). It was increased by mergepta at high concentrations (2.10(-4) M). Mergepta did not increase the potentiating effect of captopril. Carrageenan-oedema in normal rats was increased by captopril (10(-5) M), lisinopril (10(-5) M) and apstatin (1.4 10(-4) M. It was not modified by mergepta (10(-4) M), phosphoramidon (10 (-5) M) and diprotin A (109-3) M). Des-Arg1-bradykinin and Des-Arg9-bradykinin have low oedema-promoting effects. Captopril (10(-5) M) increased the effects of bradykinin but not those of carrageenan in kininogen-deficit Brown Norway rats. Angiotensin-converting enzyme and aminopeptidase P appear to be main kinin-inactivating enzymes in rat paws. Carboxypeptidase N, neutral endopeptidase 24.11 and dipeptidyl(amino)peptidase IV do not play a significant role in this inactivation.
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PMID:Potentiation of the pro-inflammatory effects of bradykinin by inhibition of angiotensin-converting enzyme and aminopeptidase P in rat paws. 893 68

Involvement of PAF and kinin in the endotoxin (LPS)-induced hypotension was examined in the rat strains, Brown Norway (B/N);Kitasato (Normal) and B/N-Kitasato rats, intravenous injection of 10 mg/kg LPS caused a hypotension composed on two phases (15 min and 70 min after LPS injection). However in the kininogen-deficient B/N-Katholiek rats. LPS induced only the second phase. Pretreatment with bradykinin (BK) antagonist. Hoe 140 suppressed LPS-induced hypotension of normal rats to the level of Katholiek rats. TCV 309, a PAF-antagonist, suppressed the LPS-hypotension almost completely in the both strains. The reason why the PAF-antagonist showed almost complete inhibition, could be explained by a synergism. Because concomitant injection of a small amount of BK with PAF caused potentiation of the effect of the PAF action. These results suggest that formation of endogenous BK contributes mainly to the 1st phase of LPS-hypotension, and PAF contributes to both phases, by either direct and synergistic actions.
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PMID:Role of synergistic action of PAF and kinin in bacterial endotoxin-induced hypotension in rats. 913 Nov 54

The physiological activator of protein kinase C (PKC), diacylglycerol, is formed by hydrolysis of phosphoinositides (PI) by phospholipase C (PLC) or phosphatidylcholine by phospholipase D (PLD). We have measured activation of these phospholipases by endothelin-1 (ET-1), bradykinin (BK), or phenylephrine (PE) in ventricular myocytes cultured from neonatal rat. The stimulation of PI hydrolysis after 10 min by 0.1 microM ET-1 (about 12-fold) was much greater than for BK or PE (each about four-fold), and did not correlate with translocation of nPKC delta or nPKC epsilon (Clerk A. Bogoyevitch MA. Andersson MB. Sugden PH, 1994. J Biol Chem 269: 32848-32857: Clerk A, Gillespie-Brown J, Fuller SJ, Sugden PH, 1996. Biochem J 317: 109-118). However, ET-1 and BK stimulated a similar rapid increase in [3H]InsP, formation (< 30 s), which was much greater than that seen with PE. This early phase correlated with PKC translocation. Acute or chronic exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA) or treatment with Ro-31-8220 showed that the stimulation of PI hydrolysis by PE, but not ET-1 or BK, was inhibited by activation of PKC. Furthermore, ET-1 and BK heterologously desensitized the stimulation of PI hydrolysis by PE, ET-1 or BK homologously uncoupled their own receptors from [3H]InsP3 formation, but there was no evidence of heterologous desensitization with these two agonists. Anomalously, chronic exposure to TPA increased the stimulation of PI hydrolysis by BK, but this probably resulted from an increase in BK receptor density. PLD was also rapidly activated by TPA. ET-1, BK or PE. Experiments with Ro-31-8220 showed that the stimulation of PLD by ET-1 and BK was mediated through activation of PKC. We discuss the characteristics of the activation of PI hydrolysis and PLD by ET-1, BK, and PE with respect to the translocation of PKC.
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PMID:Regulation of phospholipases C and D in rat ventricular myocytes: stimulation by endothelin-1, bradykinin and phenylephrine. 922 Mar 45

Acidic fibroblast growth factor causes an acute and transient nitric oxide-dependent hypotensive effect in experimental animals. However, this response is not found, or is very small, in vitro. We hypothesized that plasma mediators, such as kinins, are involved in aFGF-induced hypotension. We studied the hypotensive effect of intravenous aFGF (1 microg) in control Wistar rats, and compared this response to that in Wistar rats treated with a bradykinin receptor antagonist Na-adamantaneacetyl-D-Arg-(Hyp3,Thi5,8,D-Phe7]-brad yki nin), in kininogen-deficient Brown-Norway-Katholiek (BNK) rats, and in rats depleted of kininogen after repeated treatment with ellagic acid. FGF was administered in the jugular vein and mean arterial pressure was measured through a femoral artery catheter. Following treatment with the bradykinin receptor antagonist, the hypotensive effect of aFGF was reduced 38% with 58 microg of antagonist and by 60% with the 420 microg dose (9 +/- 1 vs 22 +/- 3mm Hg, p<0.01). Mean blood pressure decrease was 12 +/- 1 in BNK rats (p<0.01, vs control) and 10 +/- 2 mm Hg in kininogen-depleted ellagic acid-treated rats (p<0.05, vs control). These findings implicate kinins as necessary mediators for the hypotensive effect of aFGF in vivo. A full hypotensive effect of aFGF requires sufficient amounts of kininogens, the precursor molecules of kinins, as well as bradykinin receptors.
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PMID:Kinins are implicated of the hypotensive effect of acidic fibroblast growth factor. 923 5

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

The nature of all of the peptides critical to the mechanism(s) of the antihypertensive action of neutral endopeptidase (NEP) inhibitors is still unclear, but bradykinin is thought to be one such peptide. This study was designed to assess the effectiveness of an NEP inhibitor in deoxycorticosterone acetate (DOCA)-salt treated kininogen-deficient Brown Norway Katholiek (BN-Ka) rats. Oral administration of BP102 (10-100 mg/kg), an NEP inhibitor, increased urine volume and urinary sodium excretion in a dose-dependent manner in anesthetized Sprague-Dawley rats. DOCA-salt hypertension was induced in both BN-Ka and Brown Norway Kitasato (BN-Ki) rats after left nephrectomy. The development of DOCA-salt hypertension in normal BN-Ki rats was prevented, and that in BN-Ka rats was also significantly reduced, by an 8-day administration of BP102. When BP102 was administered for 5 weeks, the high blood pressure of DOCA-salt treated BN-Ka rats was markedly lowered, and their heart weights were reduced. These results suggest that kinins play no role in the antihypertensive effect of this inhibitor and that other factors may be involved in this effect.
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PMID:Effects of a neutral endopeptidase inhibitor, BP102, on the development of deoxycorticosterone acetate-salt hypertension in kininogen-deficient Brown Norway Katholiek rats. 963 1


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