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PubMed1988

Increase in vascular permeability of rat and guinea pig skin by T-kinin.

The vascular permeability-increasing response to T-kinin in rat and guinea pig skin was investigated. The vascular permeability was measured with 125I-labeled bovine serum albumin [( 125I]BSA) as a tracer. Plasma exudation rapidly occurred 0-15 min after the intradermal injection of T-kinin. T-kinin in doses of 0.3, 1, and 3 nM/spot significantly increased the vascular permeability in a dose-dependent manner. The vascular response of T-kinin is similar to that of bradykinin. On the other hand, T-kinin analogs, D-Ile-Ser-bradykinin and Ile-D-Ser-bradykinin only weakly enhanced the vascular permeability. Prostaglandin E1, forskolin, and the angiotensin-converting enzyme inhibitor, SQ-14225, potentiated the T-kinin-induced plasma exudation. Cyproheptadine and indomethacin did not affect the T-kinin-induced response. The results suggest that T-kinin will play an important role in increasing vascular permeability associated with inflammation.

Alprostadil↗
PubMed1987

Sex-related difference of kinin level in rat pituitary gland.

The kinin level in the pituitary glands was compared in adult male and female rats. A sex-related difference in the bradykinin (BK)-like immunoreactivity was found in the posterior lobe. The posterior pituitaries of female rats contained a higher concentration of the immunoreactive kinin than those of males. Ovariectomy of female rats resulted in the disappearance of a sex difference in the posterior kinin level and about a 3-fold increase in the anterior one. Orchidectomy of adult male rats failed to alter the kinin levels in both lobes. Moreover, the constitution of pituitary kinins was determined using HPLC. The pituitary kinins consisted of BK, Lys-BK (L-BK) and Met-Lys-BK (ML-BK) in different proportions in both lobes of male and female rats. The gonadectomy altered the proportions of these kinins. These results suggest that the pituitary kinin system may be regulated by circulating gonadal steroid hormones.

Animals↗
PubMed1996

T-kinin is resistant to hydrolysis by angiotensin I-converting enzyme.

Several enzymes of are capable of cleaving kinins at either the N- or C-terminal end. In this work, we investigated the hydrolysis of T-kinin (TK) and bradykinin (BK) by carboxypeptidase B (CpB) and angiotensin I-converting enzyme (ACE). The kinins were incubated with the enzymes in Tyrode solution kept at 37 degrees C for 25 min. The kinin residual activity in the incubation medium was bioassayed on the isolated guinea pig ileum. BK (5 micrograms/ml) and TK (5 micrograms/ml) were rapidly and similarly degraded by CpB (0.088 mU/ml) since half of both kinins was inactivated within 5 min of incubation. At 25 min of incubation with CpB the TK and BK-like activities were 20.8 +/- 3.9 (1.04 +/- 0.20 micrograms/ml) and 31.8 +/- 5.0% (1.59 +/- 0.25 micrograms/ml) of the initial kinin concentrations, respectively. BK was also rapidly inactivated by ACE (5 mU/ml) while TK activity was unaffected. At 25 min the BK and TK residual activities corresponded to 39.4 +/- 2.5 (1.97 +/- 0.13 micrograms/ml) and 93.8 +/- 9.2% (4.69 +/- 0.46 micrograms/ml) of the initial kinin concentrations, respectively. It was concluded that TK, a kinin elongated at the N-terminal position, is resistant to ACE degradation.

Bradykinin↗
PubMed2002

Diabetes modulates the expression of glomerular kinin receptors.

The localization of kinin receptors within the kidney implicates this system in the regulation of glomerular hemodynamics. We reported that diabetes alters the activity of the renal kallikrein-kinin system, and that these alterations contribute to the development of microvascular complications of diabetes. The present study examined the influence of diabetes on the expression of glomerular B1 and B2-kinin receptors, and assessed the cellular signaling of kinin receptor activation. Rats made diabetic with streptozocin (85 mg/kg), displayed plasma glucose levels in the range of 350-500 mg/dl. At 3, 7, and 21 days, B1 and B2-kinin receptor mRNA levels were measured in isolated glomeruli from control and diabetic rats by RT-PCR. Glomeruli revealed a differential pattern of expression between the two kinin receptors. The constitutively expressed B2-receptor was increased three-fold at day 3, but returned to normal levels at day 7; whereas, the inducible B1-receptor was maximally expressed (20-fold) at day 7 and remained elevated (10-fold) at day 21. To test whether the induction of kinin receptors by diabetes translates into increased responsiveness, we measured mitogen-activated protein kinase (MAPK) phosphorylation (p42, p44) in glomeruli isolated from control and diabetic rats stimulated with B1-receptor agonist (des-Arg9-bradykinin, 10(-8) M). A three-fold increase in phosphorylation of MAPK was observed in response to B1-receptor agonist challenge in glomeruli isolated form diabetic rats compared to controls. These findings demonstrate for the first time that glomerular kinin receptors are induced by diabetes, and provide a rationale to study the contribution of these receptors to the development of glomerular injury in diabetes.

Animals↗
PubMed1999

Pharmacological and molecular evidence for kinin B1 receptor expression in urinary bladder of cyclophosphamide-treated rats.

1. In the present study, we developed an experimental model of cystitis induced by cyclophosphamide (CYP). In order to characterize des-Arg9-BK-induced contraction on the urinary bladder (UB) during the development of inflammation and to quantify kinin B1 receptor gene expression using a quantitative RT - PCR technique. 2. In the presence of peptidase inhibitors captopril (10 microM), DL-thiorphan (1 microM) and DL-2-mercaptomethyl-3-guanidino-ethylthiopropanoic acid (MERGEPTA 5 microM), bradykinin (BK) (0.3 - 3,000 nM) evoked a concentration-dependent contraction of rat UB which was not different between the CYP- and vehicle-treated groups. Unlike BK, des-Arg9-BK (0.3 - 100,000 nM) did not contract UB from vehicle-treated rats but contracted vigorously bladder strips from CYP-treated rats 14, 24 and 168 h after treatment. In UB of 24 h treated rat, the pD2 value of des-Arg9-BK was 7.3+/-0.1. 3. The cyclo-oxygenase inhibitor indomethacin (3 microM) reduced by 30% the maximal response of des-Arg9-BK. Both the kinin B1 receptor antagonists des-Arg9-[Leu8]BK (10 microM) and des-Arg10-Hoe 140 (10 microM) produced a rightward shift of the concentration-response curve to des-Arg9-BK yielding pKB values of 6.8+/-0.2 and 7.2+/-0.1, respectively, whilst the kinin B2 receptor antagonist Hoe 140 (1 microM) had no effect. 4. After CYP treatment, mRNA coding for the kinin B1 receptor appeared predominantly in UB. In this organ, the induction was progressive, reaching a maximum 48 h after CYP treatment. 5. In conclusion, the present study provides strong evidence for an induction of kinin B1 receptors in UB of CYP-treated rats. This was associated at a molecular level with an increase in mRNA expression of the gene coding for the kinin B1 receptor. This kinin receptor displayed the whole features of a classical rat kinin B1 receptor.

Acrolein↗
PubMed1992

Effect of kinin receptor antagonists on renal hemodynamic and natriuretic responses to volume expansion.

The role of kinins in the natriuretic and papillary blood flow (PBF) responses to intravenous administration of 0.9% sodium chloride solution equal to 5% of body weight over 30 min was evaluated using a B1-kinin receptor antagonist (des-Arg9, [Leu8]bradykinin, 2.5 micrograms/min i.v.) and a B2-kinin receptor antagonist (D-Arg, [Hyp3,Thi5,8,D-Phe7]bradykinin, 2.5 micrograms/min i.v.). In control rats, PBF increased 43 +/- 5% after the volume expansion with saline. Administration of the B1-kinin receptor antagonist had no significant effect on basal PBF or the rise in PBF produced by volume expansion. In contrast, administration of the B2-kinin receptor antagonist decreased basal PBF by 18 +/- 3% and prevented the rise in PBF during volume expansion. Urine osmolality was lower in the rats treated with the B1-antagonist and higher in rats infused with the B2-kinin antagonist than in control animals after volume expansion (587 +/- 47 and 1,082 +/- 83 vs. 907 +/- 124 mosmol/kgH2O, respectively). The initial natriuretic response during the first 30 min after volume expansion was similar in rats given vehicle or the kinin antagonists. However, cumulative sodium excretion over the 2-h course of the experiment was significantly lower in the rats given the B2-receptor antagonist than in control rats (92 +/- 7 vs. 101 +/- 9% of the administered load). The B1-kinin receptor antagonist had no effect on cumulative sodium excretion; however, glomerular filtration rate was 30% lower in rats receiving the B1-antagonist than in control rats after volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effect of T-kinin on microvascular permeability and its modulation by peptidases in rat airways.

T-kinin (Ile-Ser-bradykinin), the product of T-kininogen, has been found in rat plasma during systemic inflammation, but the effect of this kinin on airway inflammatory response is unknown. We examined the effect of T-kinin on vascular permeability in airways of anesthetized rats in vivo by using photometric measurement of the extravasated Evans blue. Intravenous injection of T-kinin (0.1-10 mumol/kg) increased dye extravasation in a dose-dependent manner, with 134% for trachea and 117% for bronchi by 1 mumol/kg. Pretreatment with bradykinin B2-receptor antagonist Hoe-140 (100 nmol/kg), but not the B1-receptor antagonist des-Arg9-Leu8-bradykinin (5 mg/kg), abolished plasma extravasation evoked by T-kinin (1 mumol/kg). NK1 tachykinin-receptor antagonist CP-99994 (4 mg/kg) did not affect T-kinin-induced vascular leakage. Pretreatment with captopril (2.5 mg/kg), angiotensin-converting enzyme inhibitor, potentiated T-kinin (100 nmol/kg)-induced plasma extravasation, whereas phosphoramidon (2.5 mg/kg), a neutral endopeptidase inhibitor, had no effect. We conclude that T-kinin produces airway vascular extravasation via stimulation of B2 receptors. The effect is modulated by endogenous angiotensin-converting enzyme and is not mediated via activation of sensory nerve.

Amino Acid Sequence↗
PubMed2007

Kinin infusion prevents renal inflammation, apoptosis, and fibrosis via inhibition of oxidative stress and mitogen-activated protein kinase activity.

The progression of renal disease displays several characteristics, including proteinuria, apoptosis, inflammation, and fibrosis. In this study, we investigated the effect of long-term infusion of kinin in protection against salt-induced renal damage in Dahl salt-sensitive rats. Dahl salt-sensitive rats were fed a high-salt diet for 2 weeks and were then infused with bradykinin (500 ng/h) via subcutaneously implanted minipumps for 3 weeks. Kinin infusion attenuated salt-induced impaired renal function as evidenced by reduced proteinuria, serum creatinine, and blood urea nitrogen levels without apparent effect on blood pressure. Morphological analysis indicated that kinin administration reduced salt-induced glomerular sclerosis, tubular dilatation, luminal protein cast formation, and interlobular arterial thickness. Kinin also significantly lowered collagen I, III, and IV deposition and their mRNA levels. Moreover, kinin reduced interstitial monocyte/macrophage accumulation, as well as tubular cell apoptosis and caspase-3 activity. Protection of renal injury by kinin was associated with increased renal NO levels and reduced nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate oxidase activities and superoxide generation. Suppression of oxidative stress by kinin was accompanied by reduced transforming growth factor-beta1 protein and mRNA levels, as well as decreased phosphorylation of mitogen-activated protein kinases. This is the first study to demonstrate that kinin infusion can directly protect against salt-induced renal injury without blood pressure reduction by inhibiting apoptosis, inflammation, and fibrosis via suppression of oxidative stress, transforming growth factor-beta1 expression, and mitogen-activated protein kinase activation.

Animals↗
PubMed2001

Effect of Chronic Blockade of the Kallikrein-Kinin System on the Development of Hypertension in Rats.

-The kallikrein-kininogen-kinin system is an important vasodilator and vasodepressor component of the cardiovascular system. Acting mainly through B(2) receptors, kinins may counterbalance the pressor effect of angiotensin II, salt, and mineralocorticoids plus salt. Using rats lacking the bradykinin precursors low- and high-molecular-weight kininogen or a B(2) kinin receptor antagonist (icatibant), we investigated whether absence or blockade of the kallikrein-kinin system alters blood pressure (BP) in rats given (1) chronic infusion of Ang II, (2) a normal or high salt diet, or (3) chronic administration of deoxycorticosterone acetate (DOCA) plus salt. We confirmed the genotype and phenotype of Brown Norway Katholiek rats (BNK) and found that they had a G-to-A point mutation on the kininogen gene compared with Brown Norway (BN) and Sprague-Dawley (SD) rats, very low levels of high-molecular-weight kininogen (17+/-3 ng/mL) compared with BN and SD (1814+/-253 and 2397+/-302 ng/mL, respectively; P:<0.01), and plasma low-molecular-weight kininogen concentrations below detectable limits compared with 1773+/-74 and 1781+/-140 ng/mL for BN and SD, respectively. Basal BP was the same in BNK and BN. Chronic infusion of icatibant did not alter BP in BN or Wistar rats. At doses that blocked the acute effect of bradykinin, icatibant did not potentiate the pressor effect of a chronic subpressor or pressor dose of angiotensin II in male and female Wistar rats nor that of a high salt diet (2%) plus unilateral nephrectomy in male Wistar rats. Moreover, blockade of the kallikrein-kininogen-kinin system in either BN rats given a very high dose of icatibant or kinin-deficient rats (BNK) did not potentiate the pressor effect of angiotensin II (nonpressor dose) or a high salt (3% NaCl) diet given for 2 weeks. Established DOCA-salt hypertension was not exaggerated in rats treated with icatibant but was partially attenuated by ramipril (1.5 mg. kg(-)(1). d(-)(1) for 7 days; P:<0.002). This antihypertensive effect was abolished by icatibant (P:<0.002, ramipril versus ramipril plus icatibant). These results suggest that endogenous kinins do not participate in the maintenance of normal blood pressure or antagonize the development of hypertension induced by chronic infusion of angiotensin II, a high salt diet, or DOCA-salt. However, kinins appear to play an important role in the antihypertensive effect of angiotensin-converting enzyme inhibitors in DOCA-salt hypertension.

Journal Article↗
PubMed1990

Bradykinin stimulates the production of cyclic GMP via activation of B2 kinin receptors in cultured porcine aortic endothelial cells.

The production of endothelium-derived relaxing factor(s) in response to kinins was investigated in cultured porcine aortic endothelial cells. The production was estimated by the measurement of the accumulation of cyclic GMP, a response which can be attributed to activation of the soluble guanylate cyclase of the endothelial cells by endothelium-derived relaxing factor(s). Bradykinin increased markedly the levels of cyclic GMP in endothelial cells without affecting those of cyclic AMP. The bradykinin-stimulated production of cyclic GMP was transient and concentration-dependent. Kallidin (an agonist at B2-kinin receptors) but not des-Arg9 bradykinin and des-Arg10 kallidin (agonists at B1 kinin receptors) also increased, in a concentration-dependent manner, the content of cyclic GMP. The B2 kinin receptor antagonist, D-Arg0 [Hyp3, D-Phe7]bradykinin but not the B1 kinin receptor antagonists Leu8-des-Arg9 bradykinin and Leu9-des-Arg10 kallidin inhibited the production of cyclic GMP upon stimulation of the endothelial cells with either bradykinin or kallidin. Both the basal and kinin (bradykinin and kallidin)-stimulated productions of cyclic GMP were reduced by hemoglobin and potentiated by superoxide dismutase. Methylene blue also reduced kinin-stimulated production of cyclic GMP. These findings suggest that cultured porcine aortic endothelial cells possess B2 kinin receptors which are associated with the production and/or release of endothelium-derived relaxing factor(s). The endothelium-derived relaxing factor(s) produced in turn enhances the activity of soluble guanylate cyclase and induces the accumulation of cyclic GMP.

Animals↗
PubMed1993

B1 and B2 kinin receptors on cultured rabbit superior mesenteric artery smooth muscle cells: receptor-specific stimulation of inositol phosphate formation and arachidonic acid release by des-Arg9-bradykinin and bradykinin.

In this study we investigated receptor-specific cellular signals elicited by kinin agonists in cultured rabbit superior mesenteric artery smooth muscle cells. Kinins promoted an increase in inositol phosphate formation and arachidonic acid release in these cells. The responses elicited by des-Arg9-bradykinin (des-Arg9-BK), a B1 kinin agonist, were antagonized by des-Arg9[Leu8]-BK, a B1 kinin antagonist, but not by D-Arg0[Hyp3,D-Phe7]-BK, a B2 kinin antagonist. In contrast, the responses elicited by BK, a B2 kinin agonist, were antagonized with the opposite antagonist specificity. Lys-BK or kallidin displayed a biphasic concentration-response relationship and each response phase was selectively antagonized by each of the above antagonists. Des-Arg9-BK, at 1 microM, promoted a sustained increase primarily in the level of inositol monophosphate which was partially dependent on extracellular Ca++, whereas 1 microM BK promoted a transient increase in the levels of inositol trisphosphate, inositol bisphosphate and inositol monophosphate, and the formation of inositol monophosphate was only marginally dependent on extracellular Ca++. Pretreatment with 0.1 microM phorbol 12-myristate-13-acetate resulted in inhibition of both des-Arg9-BK- and BK-promoted inositol phosphate formation. ADP-ribosylation by pertussis toxin (100 ng/ml) had no effect on the inositol phosphate response elicited by either of these agonists. The major finding in this study is that pharmacologically typical B1 and B2 kinin receptors are both coupled to inositol phospholipid metabolism and arachidonic acid release. These cells should provide an excellent system for further studies of the function and regulation of B1 and B2 kinin receptors.

Animals↗
PubMed1996

Kinins in the cardiovascular system.

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.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

The plasma and tissue kininogen-kallikrein-kinin system: role in the cardiovascular system.

Bradykinin and Lys-bradykinin are potent peptide mediators implicated in several physiopathological effects in mammals. They act through activation of G-protein-coupled constitutive B(2) or inducible kinin B(1) receptors linked to signaling pathways involving increased intracellular Ca(++) concentrations and/or release of mediators including arachidonic acid metabolites, NO and EDHF. In the cardiovascular system, the kallikrein-kinin system exerts a fine control of vascular smooth muscle tone and arterial blood pressure, and plays a significant cardioprotective effect. This has been lately confirmed in experimental studies employing transgenic mice overexpressing human tissue kallikrein and animals with knockout of kinin B(1) and B(2) receptor gene. Disturbances in this system are associated with arterial hypertension, myocardial ischaemia and other clinical complications. Inhibitors of kininase II (angiotensin-converting enzyme) have been prescribed successfully to patients with cardiovascular diseases, but there is still a great interest in developing drugs or pharmacological strategies that augment the activity of kininogen-kallikrein-kinin system in pathological conditions. Delivery of adenovirus vector containing the human tissue kallikrein gene (gene kallikrein therapy) has emerged as a great potential to satisfy these conditions. This review provides a summary of plasma and tissue kallikrein-kinin system, focusing on the pharmacological properties, kinin receptors and drugs reported to interfere with their actions. The modulatory effects of the kallikrein-kinin system on cardiovascular system, particularly in regulating smooth muscle tone and arterial blood pressure and in preventing myocardium ischaemia have also been explored in the review.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

[An experimental model of depletion of the blood kallikrein-kinin system].

A new way of kallikrein-kinin system exhaustion in experiments on animals is suggested. This approach consists in a simultaneous rise in the activity of kinin formation and destruction. It is shown that insignificant activation of the kallikrein system and kininase activity leads to activation of the kinin system and rise in active kinin levels. A 1.5-3-fold increase in the total activity of kallikrein and a simultaneous 3-6-fold increase in kininase activity cause exhaustion of the blood kallikrein-kinin system in 2 hours and makes active kinin formation impossible by the body's requirements when the synthesis of kinin system components is maintained.

Animals↗
PubMed1986

Mechanism and significance of kinin formation in nephrotic syndrome.

There were few reports demonstrating behavior of kinin and kininogen in the nephrotic syndrome. In this paper, coagulation factors related to contact activation, such as factor XII (FXII), factor XI (FXI), prekallikrein (PK), high molecular weight kininogen (HMWKG), and kinins were measured in 15 cases of nephrotic syndrome, and clinical significance of these results were discussed. Plasma FXII activity was markedly decreased in the onset and florid stages of nephrotic syndrome, and this decrease was not correlated with plasma albumin level, which suggested marked activation of this factor in these stages. However, the decrease of PK was slight at the above stages. Activations of contact factors were not parallely occurred with the marked consumption of FXII. Plasma kinin activity was not increased in the onset and critical stages of the nephrotic syndrome but increased in the convalescent and chronic stages, while HMWK level was maintained higher than normal throughout the course. Plasma angiotensin-converting enzyme (kininase II) activity was increased in the early stage and decreased lower than normal during the course of the disease. It was concluded that kinin formation in the nephrotic syndrome was not due to the activation of intrinsic coagulation system but due to release of kinin from low molecular weight kininogen. This increased level of kinin activity in convalescent and chronic stage may be related to the healing process during the course of this syndrome. Low kinin activity in the early stage of this disease might be also explained by increased kininase II activity.

Adolescent↗
PubMed1979

How do kinins affect vascular tone?

Because kinins affect vascular tone, it is assumed that kinins act directly on smooth muscle. However, a direct interaction is difficult to conceive. Vessels containing smooth muscle are lined by a continuous endothelium with tight junctions. In addition, kinins act on endothelial cells to cause the release of prostaglandin-related substances; possibly through receptors. Furthermore, endothelial cells have a great capacity for hydrolyzing kinins to inactive products. Hence, even invoking active transport, less than 1% of kinins might be expected to reach the first layer of smooth muscle cells. However, kinins may not act directly on smooth muscle as endothelial cells and smooth muscle cells form specialized cell contacts. Myoendothelial junctions occur, and we have shown, in pulmonary arterioles, that smooth muscle cells send large numbers of projections into the cytoplasm of the endothelial cells. In addition, smooth muscle cells attach directly to the abluminal surface of endothelial cells, as do pericytes. Thus, there is a morphologic basis by which kinins can affect tone of smooth muscle without acting directly on smooth muscle cells.

Animals↗
PubMed1987

Receptors mediating the increase in vascular permeability to kinins: comparative studies in rat, guinea-pig and rabbit.

The effect of bradykinin (BK) and a variety of kinin analogues and modified kinin fragments were assessed in several models representing the vascular permeability aspect of the inflammatory response. The rank order of potency of various kinin analogues to increase paw volume and skin vascular permeability in rats was sigma-cyclo-(Lys1-Gly6)-BK = sigma-cyclo-kallidin much greater than BK greater than kallidin = methionyl-lysyl-BK much greater than des-Arg9-BK. The same order was seen for skin responses in day 21, rheumatoid-arthritic rats. Mepyramine, 10 mg X kg-1 almost completely inhibited rat skin vascular responses to histamine, had no effect on BK and produced a small but significant inhibition of the responses to both cyclic-kinins. A different rank order of potency for the kinins was produced in both the guinea-pig and rabbit skin; this being kallidin greater than methionyl-lysyl-BK greater than BK much much greater than sigma-cyclo-(Lys1-Gly6)-BK = sigma-cyclo-kallidin greater than des-Arg9-BK. Neither of the cyclic kinins antagonised BK-induced increases in skin vascular permeability in guinea-pig or rabbit. Two modified kinin fragments, D-Pro-Phe-Arg-paranitroaniline and D-Pro-Phe-Arg-heptylamide, which have previously been demonstrated to be putative B2 receptor antagonists on in vitro tissues, enhanced the effect of BK in rat skin and when injected alone produced dose-related increases in skin vascular permeability in normal and rheumatoid-arthritic rats both having approximately half the potency of BK.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Inactivation of kallikrein and kininases and stabilization of whole rat brain kinin levels following focused microwave irradiation.

Focused microwave irradiation was employed to stabilize endogenous whole rat brain bradykinin levels prior to a simple extraction procedure. Skull microwave exposure (2450 MHz, 3.8 kW., 2.45 sec) resulted in inactivation to less than 5% of control of whole brain kallikrein and kininase activity. Using this adequate exposure duration whole rat brain kinin levels as measured by a sensitive radioimmunoassay were approximately 0.6 pmol/g (wet weight). Further purification of irradiated brain extracts using HPLC revealed that immunoreactive kinin eluted as a single peak that co-chromatographed with authentic bradykinin. Microwave fixation duration of 1.25 sec yielded greatly increased levels of immunoreactive kinin which following HPLC purification eluted in two peaks, corresponding to authentic bradykinin and T-kinin, respectively. The tissue injury resulting from incomplete microwave fixation resulted in the release of kinins. This excess immunoreactive kinin may be derived from cerebral blood, since the predominant form of kinin-generating protein in plasma is T-kininogen.

Animals↗