Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since converting enzyme and kininase II are identical enzymes and probably influences both, the biosynthesis of Ang II and the metabolism of bradykinin we investigated the effects of bradykinin, desArg-bradykinin and some bradykinin antagonists (desArg[9]-Leu[8]-bradykinin, HOE S 890307) on the sympathetic outflow of pithed SHR or Brown-Norway-Rats before and after acute or chronic inhibition of the converting enzyme by ramipril. bradykinin increased dose dependently the noradrenaline and adrenaline release in particular when the converting enzyme was inhibited. DesArg-bradykinin caused a dose-dependent increase in adrenaline release only after converting enzyme inhibition. The bradykinin-antagonists led to an increase in adrenaline release during ramipril administration. The weak but significant stimulation of adrenaline release by the bradykinin antagonists after converting enzyme inhibition might be due to unspecific actions on the adrenal medulla possibly induced by histamine release from mast cells.
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PMID:Modulation of presynaptic sympathetic activity by kinins and related compounds: influence of converting enzyme inhibition. 146 84

Paw oedema in the rat by carrageenin and kaolin partially caused by Hageman factor activation was potentiated by the new angiotensin converting enzyme (ACE) inhibitor 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl-L-alanyl]-(lS,3S,5S)-2- azabicyclo[3.3.0]octane-3-carboxylic acid] (ramipril, Hoe 498) due to its inhibition of kininase II which results in increased bradykinin levels. A dose of 1 microgram ramipril injected into the hind paw of Sprague-Dawley rats concomitantly with, or 1 mg/kg given orally 30 min before administration of the irritants, led to significantly increased inflammatory reactions. The same effects were observed when ramipril was administered 3 h after carrageenin. In the kallikrein-kinin-deficient Brown-Norway rat strain Mai Pfd/f, ramipril did not significantly alter the paw oedema induced as described above. In addition, pretreatment of Sprague-Dawley rats with 10 mg/kg i.v. bromelains completely prevented the potentiation of inflammation by ramipril. Paw oedema provoked by the Hageman factor non-activators serotonin, dextran, ovalbumin and anti-rat IgG was not potentiated by ramipril. The chronic adjuvant arthritis in Lewis rats was not influenced by daily oral treatment with 0.1-3 mg/kg ramipril. Thus, in the rat only those inflammatory reactions involving kinins, presumably generated by Hageman factor activators, are potentiated by ramipril and presumably by other ACE-inhibitors.
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PMID:Influence of the new angiotensin converting enzyme inhibitor ramipril on several models of acute inflammation and the adjuvant arthritis in the rat. 302 36

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

1. Subcutaneous injection of sodium deoxycholic acid into the anterior of the back of male ddY mice elicited dose-dependent scratching of the injected site with the forepaws and hindpaws. 2. Up to 100 microg of sodium deoxycholic acid induced no significant increase in vascular permeability at the injection site as assessed by a dye leakage method. 3. Bradykinin (BK) B2 receptor antagonists, FR173657 and Hoe140, significantly decreased the frequency of scratching induced by sodium deoxycholic acid. 4. Treatment with aprotinin to inhibit tissue kallikrein reduced the scratching behaviour induced by sodium deoxycholic acid, whereas treatment with soybean trypsin inhibitor to inhibit plasma kallikrein did not. 5. Although injection of kininase II inhibitor, lisinopril together with sodium deoxycholic acid did not alter the scratching behaviour, phosphoramidon, a neutral endopeptidase inhibitor, significantly increased the frequency of scratching. 6. Homogenates of the skin excised from the backs of mice were subjected to gel-filtration column chromatography followed by an assay of kinin release by trypsin from each fraction separated. Less kinin release from the fractions containing kininogen of low molecular weight was observed in the skin injected with sodium deoxycholic acid than in normal skin. 7. The frequency of scratching after the injection of sodium deoxycholic acid in plasma kininogen-deficient Brown Norway Katholiek rats was significantly lower than that in normal rats of the same strain, Brown Norway Kitasato rats. 8. These results indicate that BK released from low-molecular-weight kininogen by tissue kallikrein, but not from high-molecular-weight kininogen by plasma kallikrein, may be involved in the scratching behaviour induced by the injection of sodium deoxycholic acid in the rodent.
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PMID:Reduction of sodium deoxycholic acid-induced scratching behaviour by bradykinin B2 receptor antagonists. 1005 Nov 36

Involvements of kinin and prostaglandin and their interaction in noxious thermal stimuli were investigated in noninflamed and inflamed rats. The nociceptive response was evaluated from the escape latency of foot withdrawal to the thermal stimuli with a beam of light. The escape latency in kininogens-deficient Brown Norway (B/N-) Katholiek rats was significantly longer than that in the normal strain, B/N-Kitasato rats. The latency in B/N-Kitasato rat was prolonged by administration of a bradykinin (BK) B2 receptor antagonist, FR173657 (30 mg/kg, p.o.), whereas it was shortened by pretreatment with a kininase II inhibitor, captopril (10 mg/kg, i.p.). Both agents did not affect the latency in B/N-Katholiek rats. In normal Sprague-Dawley (SD) rat, administration of indomethacin did not change the escape latency against the thermal stimuli. In contrast, administration of indomethacin or a relatively cyclooxygenase-1-selective inhibitor, mofezolac (10 mg/kg, p.o.) significantly reduced numbers of writhing reaction in mice induced by acetic acid solution. Injection of lipopolysaccharide (1 mg/kg, i.v.) resulted in shortening escape latency at 8 h after the injection in B/N-Kitasato rats. This hyperalgesia could be reversed by pretreatment of the rats with indomethacin, a cyclooxygenase-2-selective inhibitor JTE-522 (10 mg/kg, p.o.), or FR173657, but not with mofezolac. The hyperalgesia was not seen in B/N-Katholiek rats. These results indicate that kinin has major participation in peripheral skin thermal nociception under noninflamed condition, although cyclooxygenases may have little participation. Prostaglandins produced by cyclooxygenase-2 could coordinate with BK to elicit hyperalgesia during inflammation induced by lipopolysaccharide.
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PMID:Role of kinin and prostaglandin in cutaneous thermal nociception. 1248 14

In the framework of an EU study entitled "Respiratory Allergy and Inflammation Due to Ambient Particles" (RAIAP), various collected particulate matter samples were to be tested for their adjuvant potency in two animal models of allergy. A pollen allergy model in the Brown Norway (BN) rat and an ovalbumin model in the BALB/c mouse were used in this study to compare the discriminatory value of these two models and to evaluate them for later studies of collected RAIAP-samples. Two different sources of diesel exhaust particles (DEP I and DEP II ), a residual oil fly ash source (ROFA), and two sources of ambient particles (Ottawa dust, EHC-93, and road tunnel dust, RTD) were tested. Rats were sensitized intratracheally with Timothy grass pollen (Phleum pratense, 200 microl, 10 mg/ml) on d 0, challenged on d 21, and examined on d 25. Mice were sensitized intranasally at d 0 and 14, challenged intranasally at d 35, 38, and 41 (50 microl, 0.4 mg ovalbumin/ml), and examined at d 42. Particulate matter (PM) was administered either during the sensitization phase only or during the sensitization and challenge phases (for mice only) or during the challenge phase only. In the pollen model, only DEP I, but not DEP II, ROFA, EHC-93, and RTD, stimulated the immunoglobulin (Ig) E and IgG1 response in serum to pollen allergens. In addition to this adjuvant effect noted, no other biomarkers in lung or bronchoalveolar lavage (BAL) revealed adjuvant activity in the pollen model. In the BAL of BN rats exposed to a combination of pollen and PM, the percentages of eosinophilic granulocytes were decreased compared to the BAL of BN rats immunized with pollen only. In the ovalbumin model, the IgE levels in serum were increased in mice after coexposure to ovalbumin and PM (including DEPI, DEPII, ROFA, EHC-93, and RTD) in the sensitization phase but not after coexposure during the challenge phase only. The inflammatory response was greater in the lung, predominantly the influx of eosinophilic granulocytes, as was observed by both histopathological examination and BAL analysis. In addition, BAL levels of inflammatory interleukin (IL)-4 were increased. Based on the IgE antibody response to ovalbumin, the ovalbumin model ranked the adjuvant capacity of the particles in the following order: RTD > ROFA > EHC-93 > DEPI > DEPII. In conclusion, the ovalbumin model is a sensitive system to detect adjuvant activity of airborne particles, whereas the pollen-induced allergy model in rat was less sensitive.
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PMID:Adjuvant activity of various diesel exhaust and ambient particles in two allergic models. 1285 33

We have previously described angiotensin I-converting enzyme (ACE) forms in urine of normotensive (190 and 65 kDa) and hypertensive patients (90 and 65 kDa, N-domain ACEs). Based on the results described above, experimental and genetic models of hypertension were investigated to distinguish hemodynamic and genetic influence on the generation of ACE profile in urine: Wistar-Kyoto and Brown Norway rats (WKY and BN), spontaneously and stroke-prone spontaneously hypertensive rats (SHR and SHR-SP), one kidney/one clip rats (1K1C), deoxycorticosterone acetate (DOCA) salt-treated and untreated rats, and enalapril-treated SHR (SHRen). Two peaks with ACE activity were separated from the urine of WKY and BN rats submitted to an AcA-44 column, WK-1/BN-1 (190 kDa), and WK-2/BN-2 (65 kDa), as described for urine of normotensive subjects. The same results were obtained for urine of 1K1C and DOCA salt-treated and untreated rats, analyzed to evaluate the influence of hemodynamic factors in the ACE profile in urine. The urine from SHR, SHR-SP, and SHRen presented 80 (S-1, SP-1, Sen-1) and 65 (S-2, SP-2, Sen-2) kDa ACE forms, differing from the urine profile of normotensive rats, but similar to that described for hypertensive patients. The presence of 80 kDa ACE in urine of SHR, SHR-SP, and SHRen and its absence in urine of experimental hypertensive rats (1K1C and DOCA salt) support the hypothesis that this enzyme could be a possible genetic marker of hypertension. Taken together, our results provide evidence that ACE forms with 90/80 kDa isolated from the urine of hypertensive subjects and genetic hypertensive animals behaves as a possible genetic marker of hypertension and not as a marker of high blood pressure.
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PMID:N-domain angiotensin I-converting enzyme with 80 kDa as a possible genetic marker of hypertension. 1290 Apr 33

Commonly consumed carbohydrate sweeteners derived from sugar cane, palm, and corn (syrups) were investigated to determine their potential to inhibit key enzymes relevant to Type 2 diabetes and hypertension based on the total phenolic content and antioxidant activity using in vitro models. Among sugar cane derivatives, brown sugars showed higher antidiabetes potential than white sugars; nevertheless, no angiotensin I-converting enzyme (ACE) inhibition was detected in both sugar classes. Brown sugar from Peru and Mauritius (dark muscovado) had the highest total phenolic content and 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity, which correlated with a moderate inhibition of yeast alpha-glucosidase without showing a significant effect on porcine pancreatic alpha-amylase activity. In addition, chlorogenic acid quantified by high-performance liquid chromatography was detected in these sugars (128 +/- 6 and 144 +/- 2 microg/g of sample weight, respectively). Date sugar exhibited high alpha-glucosidase, alpha-amylase, and ACE inhibitory activities that correlated with high total phenolic content and antioxidant activity. Neither phenolic compounds or antioxidant activity was detected in corn syrups, indicating that nonphenolic factors may be involved in their significant ability to inhibit alpha-glucosidase, alpha-amylase, and ACE. This study provides a strong biochemical rationale for further in vivo studies and useful information to make better dietary sweetener choices for Type 2 diabetes and hypertension management.
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PMID:Antidiabetes and antihypertension potential of commonly consumed carbohydrate sweeteners using in vitro models. 1859 78