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

Deoxycorticosterone acetate (DOCA)-salt hypertension was induced in Brown Norway (BN) kininogen-deficient rats (BN-Ka) and normal rats from the same strain (BN-Ki) after nephrectomy. Systolic blood pressure, which was determined by the tail-cuff method, of BN-Ki increased gradually during this treatment. In contrast, the blood pressure of mutant BN-Ka increased rapidly 2 weeks after the onset of the treatment. Urinary excretion of active kallikrein and prokallikrein increased at the same degree in rats of both strains during this treatment. Significant increase in urinary sodium excretion was observed with a tendency to increase in urine volume during the treatment in normal BN-Ki rats, whereas both parameters were essentially not increased in mutant BN-Ka rats, which could not generate urinary kinin. Aprotinin infusion by osmotic minipump to normal BN-Ki rats during the DOCA-salt treatment resulted in significant further increase in the systolic blood pressure.
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PMID:Essential role of kallikrein-kinin system in suppression of blood pressure rise during the developmental stage of hypertension induced by deoxycorticosterone acetate-salt in rats. 128 79

The Brown Norway Katholiek (B/N-Ka) strain rat is the only animal strain that demonstrates deficiency in plasma HMW- and LMW-kininogens with a low level of prekallikrein. We developed an RIA for rat HMW-kininogen, LMW-kininogen, and T-kininogen, and using them measured these proteins in B/N-Ka and normal strain (B/N-Ki) rats. Plasma level of immunoreactive as well as kinin-releasing HMW-kininogen and LMW-kininogen in B/N-Ka rats was either around 3% of their levels in the normal B/N-Ki rats. The cause of the plasma deficiency of kininogens in the B/N-Ka strain was examined by 35S-methionine uptake of primary cultures of hepatocytes from the B/N-Ki and B/N-Ka strains. The results indicated that the kininogens were synthesized in the B/N-Ka liver but not secreted into the medium. Northern blot analysis of poly A(+)RNA extracted from the livers of both strains demonstrated that the band corresponding to mRNA of HMW-kininogen was present in the mRNA from B/N-Ka liver as well as in that from the B/N-Ki one. The band was similar in size and intensity in both cases. This result confirmed the data that immunoreactive HMW-kininogen was found in the liver of B/N-Ka rats (12). Thus, the cause of plasma deficiency of HMW-kininogen in the mutant appears to be secretory defect in nature. The B/N-Ka rats showed less reactivity to the inflammatory stimulus, such as carrageenin or kaolin, but the strain expressed almost the same response as normal rats to phorbol ester (PMA) or zymosan for pleurisy induction. These results indicate that kinin may play an important role in exudation in carrageenin- and kaolin-induced edema but not in that induced by PMA or zymosan. The deficient rat strain could be useful for differentiation of the inflammatory model which shows involvement of the kinin system.
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PMID:Kininogen deficiency in the rat. 128 9

Atrial natriuretic peptide (ANP) is degraded by neutral endopeptidase (NEP) mainly in the proximal tubule of the kidneys. We studied the effects of retrothiorphan, a potent and highly specific NEP inhibitor on renal function and blood pressure (BP). A 25-mg/kg bolus injection (group bolus), or bolus injection plus infusion 25 mg/kg + 25 mg/kg/h (group infusion), was given to conscious normotensive Wistar and hypertensive DOCA-salt rats. Bolus and infusion produced increases in diuresis (110 +/- 15 vs. 103 +/- 15 vs. 42 +/- 9 microliters/min) and natriuresis (10.6 +/- 3.0 vs. 7.0 +/- 1.0 vs. 5.4 +/- 1.0 mumol/min) in normotensive rats, with a maximum change at 30 min. Change in kaliuresis was not significant. These renal effects were associated with nonsignificant increases in urinary cyclic GMP and ANP. Arterial pressure and heart rate (HR) were not affected. Bolus or infusion of retrothiorphan also induced increases in diuresis (92 +/- 16 vs. 124 +/- 13 vs. 38 +/- 6 microliters/min) and natriuresis (10.3 +/- 2.0 vs. 12.5 +/- 1.0 vs. 5.0 +/- 1.0 mumol/min) in DOCA-salt hypertensive rats, with a maximum change at 30 min. The changes in diuresis and natriuresis induced by retrothiorphan were correlated with a significant increase in urinary cyclic GMP excretion (r = 0.89, p < 0.001 and r = 0.91, p < 0.001). Urinary ANP did not change in controls but significantly increased in the treated rats; urinary immunoreactive bradykinin (BK) also tended to increase. Plasma ANP and hematocrit did not change after retrothiorphan, but plasma cyclic GMP increased significantly after infusion. Only infusion caused a decrease in arterial pressure in DOCA-salt rats (-20 mm Hg at 120 min). Renal clearance studies in DOCA-salt rats showed that retrothiorphan has a transient effect on renal hemodynamics, with increases in glomerular filtration and renal blood flow (RBF) and a decrease in renal vascular resistance (RVR). Its renal action was also tubular, with an increase in fractional sodium excretion. We also compared the effects of retrothiorphan in normotensive Brown-Norway kininogen-deficient rats (BN-Kat) and DOCA-salt hypertensive kininogen-deficient rats. The NEP inhibitor induced increases in diuresis and natriuresis in both groups, with increased urinary cyclic GMP. Urinary immunoreactive BK did not change significantly in normotensive or DOCA-salt hypertensive kininogen-deficient rats.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of the selective neutral endopeptidase inhibitor, retrothiorphan, on renal function and blood pressure in conscious normotensive Wistar and hypertensive DOCA-salt rats. 128 84

We investigated the chronic effect of bradykinin B2-receptor blockade on the antihypertensive actions of the angiotensin-converting enzyme (ACE) inhibitor ramipril in three different hypertensive rat models, the two-kidney/one-clip (2K1C) hypertensive Wistar rat, the kinin-deficient 2K1C hypertensive Brown Norway Katholieke (BN-K) rat, and the spontaneously hypertensive rat (SHR). Chronic blockade of bradykinin B2 receptors by subcutaneous infusion of the new bradykinin antagonist HOE 140 (500 micrograms/kg/day) attenuated the antihypertensive effect of ramipril only in 2K1C hypertensive Wistar rats, but not in 2K1C BN-K rats and SHR. Our data demonstrate for the first time that potentiation of endogenous kinins contributes to chronic antihypertensive actions of ACE inhibitors in experimental renal hypertension. Whether this holds also true for other forms of hypertension remains to be answered.
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PMID:Role of bradykinin in chronic antihypertensive actions of ramipril in different hypertension models. 128 37

The contribution of endogenous bradykinin to the chronic antihypertensive actions of the ACE-inhibitor, ramipril, was investigated in 2-kidney 1 clip (2K1C) hypertensive kinin-deficient Brown Norway Katholieke rats (BN-K) and 2K1C hypertensive Wistar rats (WI) as well as in spontaneously hypertensive rats (SHR). Treatment with ramipril plus the BK B2-receptor antagonist HOE 140 for 6 weeks significantly attenuated the antihypertensive effects of the ACE-inhibitor in 2K1C hypertensive WI rats, but not in 2K1C hypertensive BN-K rats and in SHR. Our data support the hypothesis that potentiation of endogenous kinins contributes to the chronic antihypertensive actions of ACE-inhibitors in experimental renal hypertension. Whether this holds also true for other forms of hypertension remains to be answered.
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PMID:Kinin contribution to chronic antihypertensive actions of ACE-inhibitors in hypertensive rats. 133 42

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

Brown Norway rat strain has been studied for mode of inheritance of its congenital deficiency in plasma high molecular weight (HMW)-kininogen and low molecular weight (LMW)-kininogen, and low plasma level of prekallikrein. We examined the genetics of the deficiency by performing a mixed breeding experiment between B/N-Katholiek (B/N-Ka, deficient) and B/N-Kitasato (B/N-Ki, normal) strains. Incidence of the deficiency was judged by the plasma level of HMW-kininogen. Plasma level of HMW-kininogen was around 50% of the normal level in all F1 generations of the hybrid between male B/N-Ka and female B/N-Ki (Exp. 1), and between female B/N-Ka and male B/N-Ki (Exp. 2). Incidence of deficiency (plasma HMW-kininogen level less than 5%) in Exp. 1 was 23.8% in male F2 and 20.0% in female F2 generations. By Exp. 2 also the incidence was 25.0% in male and 30.0% in female F2 generations. There was no significant difference of the incidence between the two experiments or sexes. These results indicate the inheritance of the kininogen-deficiency to be Mendelian autosomal recessive, the same as for the reported cases of human kininogen deficiency. Gel filtration study suggests that prekallikrein in the B/N-Ka plasma may be free form, while that in the B/N-Ki plasma may form complex with HMW-kininogen.
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PMID:Characterization of the heredity of kininogen deficiency in brown Norway Katholiek strain rats. 161 79

We studied the influence of aprotinin and soya bean trypsin inhibitor (SBTI) on the inflammatory reaction induced by the implantation of dry sponges in normal Wistar rats and in kininogen-deficient Brown Norway rats, during the first day after the implantation. In normal rats, aprotinin reduced the volume and total protein content of the exudates at 3 h but not thereafter. Aprotinin also markedly reduced the immunoreactive kinins and kallikrein in the exudates. Aprotinin did not modify the volume of the exudates of the Brown Norway rats. SBTI reduced the inflammatory reaction in both rat strains but did not significantly modify the formation of immunoreactive kinins. The inflammatory reaction developed more slowly in Brown Norway rats. The kinin system is thus involved during the first hours of the development of this acute inflammatory reaction. The anti-inflammatory effect of SBTI does not depend on the inhibition of kinin formation.
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PMID:Proteinase inhibitors, kinins and the inflammatory reaction induced by sponge implantation in rats. 169 Nov 1

Brown Norway kininogen-deficient rats had very low levels of plasma kininogens and lower levels of plasma prekallikrein, compared with those of normal rats of the same strain. Systolic blood pressure, determined by the tail-cuff method, of 5-week-old kininogen-deficient rats (106 +/- 0.4 mm Hg, n = 7) and the rate of systolic blood pressure increase with age were not different from those in normal rats. Weekly injections of deoxycorticosterone acetate (5 mg/kg s.c.) with 1% sodium chloride solution in drinking water after uninephrectomy at 7 weeks of age caused a gradual increase in the blood pressure of normal rats, reaching a plateau at 18 weeks of age, whereas that of deficient rats rose rapidly to 158 +/- 6 mm Hg 2 weeks after the start of treatment and continued to increase slightly, becoming significantly higher than normal rats at 8, 9, 10, 11, and 12 weeks of age (p less than 0.05 or 0.01). The levels of urinary prokallikrein and active kallikrein were slightly higher in deficient rats before deoxycorticosterone acetate-salt treatment but were not significantly increased after this treatment, whereas these levels in normal rats were increased 3.6- and 4.7-fold by this treatment. Urinary free kinin, collected from the ureter in untreated deficient rats, was below the detection limit. The plasma level of low molecular weight kininogen, the substrate of glandular kallikrein, was decreased in normal rats during the treatment. Continuous subcutaneous injection of aprotinin by an osmotic pump to normal rats induced significant increase in blood pressure. These results indicate that glandular kallikrein may play a suppressive role in deoxycorticosterone acetate-salt hypertension.
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PMID:Suppression of rat deoxycorticosterone-salt hypertension by kallikrein-kinin system. 171 Jun 5

The M current, IM, a voltage-dependent non-inactivating K current, was recorded in NG108-15 neuroblastoma x glioma hybrid cells, using the whole-cell mode of the patch-clamp technique. We studied inhibition of the M current by bradykinin, phorbol dibutyrate (PDBu), an activator of protein kinase C (PKC), and methylxanthines. Focal application of 0.1-5 microM bradykinin inhibited IM by about 60%; 5 nM bradykinin inhibited by about 40%. Bath application of 0.1 microM and 1 microM PDBu diminished IM to about half of the control value. Staurosporine, a PKC inhibitor, applied for 35-43 min in a concentration of 0.3 microM significantly reduced the effect of 1 microM PDBu. M current blockage by PDBu could be partly reversed by bath application of H-7 (51-64 microM), another PKC inhibitor. These observations suggest that the PDBu effect is really due to activation of PKC. The findings are compatible with the view [Brown DA, Higashida H (1988) J Physiol (Lond) 397:185-207] that the bradykinin effect on IM is mediated by PKC. However, three further observations suggest that this is only true for part of the bradykinin effect. When the suppression of IM by 1 microM PDBu was fully developed, 0.1 microM bradykinin produced a further inhibition of IM. Down-regulation of PKC by long-term treatment with PDBu reduced the effect of 0.1 microM bradykinin significantly but did not abolish it. Staurosporine (0.3 microM, applied for 31-46 min) failed to reduce the effect of 5 nM bradykinin significantly. The M current could be reversibly blocked by methylxanthines (caffeine, isobutyl-methylxanthine, theophylline) in the millimolar range, probably because of a direct action on the M channels.
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PMID:Inhibition of the M current in NG 108-15 neuroblastoma x glioma hybrid cells. 194 51


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