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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal ischemia has been implicated as a major factor in the pathogenesis of acute renal failure. Despite several differences between the intrarenal norepinephrine infusion and renal artery occlusion models, they have been assumed to be prototypic models of ischemic renal injury. In our previous studies, an intrarenal infusion of norepinephrine caused a marked reduction in inulin clearance 3 hours after infusion. This reduction could be significantly attenuated by the concurrent infusion of mannitol, furosemide, or bradykinin. The effects of these three protective agents were evaluated before and after variable durations of renal artery occlusion to establish the similarities between the models and the magnitude of versatility of these protective agents. In the renal artery occlusion model, capsular fascia was stripped to eliminate collateral flow and ensure maximal renal ischemia. Three hours after 120 minutes of renal artery occlusion (n = 7), inulin clearance returned to 5.7% +/- 2.2% (SEM) of the control values and was not statistically different from that observed in the norepinephrine model. Intrarenal infusion of mannitol, furosemide, or bradykinin prior to and during the occlusion period, however, had no protective effect. Shorter durations of renal artery occlusion were evaluated to ensure an equivalent or decreased severity of acute renal failure compared with the norepinephrine model. After 90 or 60 minutes of renal artery occlusion, the clearance of inulin returned to 10.9% +/- 3.3% (n = 8) and 31.1% +/- 8.2% (n = 4) of control values, respectively. An intrarenal infusion of mannitol, furosemide, or bradykinin still had no significant protective effect, despite the decreased insult in the 60-minute renal artery occlusion studies. In summary, these findings demonstrate fundamental differences between renal artery occlusion and the norepinephrine model of renal functional impairment, and they suggest that the insult associated with norepinephrine infusion may involve factors other than cessation of blood flow.
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PMID:Renal ischemic injury in the dog: characterization and effect of various pharmacologic agents. 643 74

A sensitive and specific radioimmunoassay for measuring urinary kinins was developed. Antibodies against bradykinin were induced in rabbits by injecting bradykinin coupled to bovine albumin. One of the antisera generated was used at a final dilution of 1:18,000 to obtain a 30% total binding of bradykinin-(8-tyrosine)-[125I]-triacetate. Synthetic bradykinin (5-1,000 pg) was used as standard in the curves. The sensitivity of the assay was 5 pg. The recovery of bradykinin added to urinary samples was 86.85 +/- 6%. The intraassay and interassay coefficients of variation were 3.3% (n = 12) and 4.4% (n = 5), respectively. The antiserum showed no cross-reactivity with oxytocin or low molecular weight kininogen and cross-reacted with kallidin (lys-bradykinin), met-kallidin, and angiotensin I, but cross-reaction with angiotensin I (2.5%) was low enough to be disregarded. The mean urinary levels of total kinins in 12 normal subjects were 23.2 +/- (SEM) 2.2 micrograms/day.
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PMID:A radioimmunoassay method for measurement of urinary kinins. 648 28

Prekallikrein and high molecular weight kininogen were measured in plasma taken from nine women during parturition. Prekallikrein decreased significantly (p less than 0.01) from 1.49 +/- 0.15 S-2302 U/ml (mean +/- SEM) in early labor to 1.26 +/- 0.13 S-2302 U/ml in the immediate postpartum period. Immunoreactive high molecular weight kininogen also significantly decreased from 76 +/- 5 micrograms/ml to 68 +/- 5 micrograms/ml one day postpartum (p less than 0.01). Both proteins rose to normal levels within two days. The data suggest that the kallikrein-kinin system is utilized during parturition.
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PMID:Human plasma prekallikrein and high molecular weight kininogen decrease during parturition. 656 99

The effect of bradykinin (BK) on renal function was examined in anesthetized dogs with or without treatment with either indomethacin or propranolol. Renal arterial infusion of BK (3 micrograms/min) in control dogs produced a sustained increase in urine flow rate (V), sodium excretion (UNaV), potassium excretion (UKV), and renal plasma flow (RPF) without a consistent change in glomerular filtration rate (GFR) or renin secretion rate (RSR). This increase in salt and water excretion and in RPF could not be blocked with indomethacin (5 mg/kg, followed by 2.1-3.2 mg/kg/h, i.v.). UNaV was 20.8 +/- 7.4 and 123.3 +/- 22.3 muEq/min (mean +/- SEM values) before and after 140 min of infusion of BK (p less than 0.005), respectively. Beta-receptor blockade with propranolol (5 mg/kg, followed by 2.8-3.4 mg/kg/h, i.v.) did not prevent the BK-induced rise in salt and water excretion, or in RPF. UNaV was 26.0 +/- 9.7 and 96.4 +/- 21.5 muEq/min before and after 140 min of infusion of BK (p less than 0.005), respectively. The data suggest that the effects of BK on renal handling of salt and water and on RPF are not mediated by either prostaglandins or beta receptors.
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PMID:Effect of bradykinin on renal function in dogs treated with indomethacin or propranolol. 707 57

We assessed the participation of endogenous bradykinin (BK) on basal blood pressure (BP) regulation in anesthetized Dahl-sensitive (DS) and Dahl-resistant (DR) rats receiving different NaCl diets. Four groups of Dahl rats were studied after 5 weeks of high (H) = 7% or low (L) = 0.4% NaCl diet (DSH, n = 9; DSL, n = 11; DRH, n = 9; DRL, n = 10). Endogenous BK activity was assessed with a continuous intraarterial (i.a.) infusion of the specific BK antagonist (B4146 100 micrograms/kg/min) for 10 min. Sensitivity to exogenous BK was tested 30 min after the end of the infusions, with bolus intraarterial (i.a.) injections of BK (0.1, 0.5, 1, and 5 micrograms). DSH had a significantly higher (p < 0.0001) basal mean BP (MBP) as compared with the three other groups: DSH = 185 +/- 7 mm Hg (mean +/- SEM), DSL = 143 +/- 5 mm Hg, DRH = 132 +/- 10 mm Hg, and DRL = 134 +/- 6 mm Hg. BK antagonist infusion increased MBP by 13.2 +/- 1.5 mm Hg in DSL rats, by 6.8 +/- 1.6 mm Hg in DRL, by 4.7 +/- 1.6 mm Hg in DRH, and by 1.1 +/- 8 mm Hg in DSH. Statistical analysis showed that the high NaCl diet significantly decreased the response to the BK antagonist in DS (p < 0.001) but not in DR rats. MBP response to exogenous BK was similar in all groups. These results show that endogenous BK has a vasodepressor effect on DS rats fed a low NaCl diet. This effect is suppressed after a high-salt diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endogenous bradykinin activity in Dahl rats. 767 63

Activation of the contact phase of coagulation has been implicated in the pathogenesis of septic shock. We wanted to determine if inhibition of plasma kallikrein can prevent arterial hypotension and liberation of kinins from kininogen, induced by an infusion of bacterial lipopolysaccharide (LPS) in anesthetized, ventilated 20-kg pigs. The LPS was given IV in a dose of 5 micrograms/kg/h for 8 hours. The plasma kallikrein inhibitor aprotinin, 537 mumol, was given IV during 8 hours, resulting in plasma levels above 10 mumol/L. Ten animals (SA) received LPS and aprotinin and ten randomized controls (SC) received LPS and saline. Kinin-containing kininogen was determined on the basis of the amount of kinin releasable in plasma samples by incubation with trypsin. Kininogen decreased to 58% +/- 4% of the baseline value without any difference between groups. This may indicate participation of other processes than degradation by plasma kallikrein in the decrease of kininogen. Arterial blood pressure was higher at 7 hours in the SA animals than in the SC group (101% +/- 11% vs. 68% +/- 8%; mean +/- SEM; p = 0.026). Fibrin monomer and C3adesArg plasma levels were attenuated by aprotinin treatment. These findings underscore the important role of the contact system in LPS shock.
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PMID:Inhibition of plasma kallikrein with aprotinin in porcine endotoxin shock. 768 84

Microvascular clearance of FITC-Dextran 150 (fluorescein isothiocyanate dextran, MW 150,000) was studied in cremaster muscles of control (BB/W-R) and diabetic (BB/W-DM) rats following daily injections of a full (FD) or a 1/2 (reduced; RD) dose of insulin. The cremaster muscle was placed in an intravital chamber and superfused with bicarbonate buffer (pH 7.4, equilibrated with 95% N2-5% CO2). A 1-hour period of stabilization was followed by the i.v. injection of FITC-dextran 150 and an equilibration period of 45 min. Suffusate samples were collected for 1 h for control measurements. Following this period, bradykinin was applied topically at a concentration of 10(-7) M. Samples were collected for a final hour for the assessment of clearance. The mean +/- SEM FITC-dextran 150 clearance values (microliter/60 min/g) for BB/W-R, BB/W-DM FD, and BB/W-DM RD were 11.5 +/- 1.8, 14.8 +/- 3.4, and 90.5 +/- 12.0, respectively. The corresponding values after topical application of 10(-7) M bradykinin were 23.7 +/- 5.9, 24.2 +/- 4.4, and 98.7 +/- 25.0. Our results indicate that bradykinin evokes a twofold increase in FITC-dextran 150 clearance in the BB/W-R (control) animals and in the BB/W-DM rats receiving full-dose insulin. In contrast, bradykinin does not further enhance the eightfold increase in FITC-Dextran 150 clearance observed in the reduced-insulin dose-treated BB/W-DM group. Thus, our data show that insulin, administered at a full dose, protects the functional integrity of microvascular perm-selectivity in diabetes mellitus.
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PMID:Microvascular clearance of macromolecules in skeletal muscle of spontaneously diabetic rats. 768 75

We wished to determine, using a novel specific antagonist of BK2, HOE 140, (a) if the angiotensin-converting enzyme (ACE) inhibitor, ramiprilat, reduces myocardial infarct size in a well-established animal model of ischemia/reperfusion with minimal coronary collateralization, and (b) if the reduction in myocardial infarct size occurred through a bradykinin-dependent mechanism Saline vehicle, ramiprilat, HOE 140, or ramiprilat plus HOE 140 (n = 6 each group), was administered intravenously (i.v.) in intact animal preparations of experimentally induced acute myocardial ischemia. Anesthetized, open-chest rabbits were instrumented for measurement of systemic hemodynamics and left ventricular pressure (LVP), from which LV + dP/dtmax was derived. Animals were subjected to 30-min left main coronary artery occlusion (marginal branch) followed by 2-h reperfusion. Ramiprilat (50 micrograms/kg) or saline was administered before reperfusion, and rabbits receiving HOE 140 were pretreated before occlusion (1 microgram/kg). In separate duration of action experiments (n = 6 each group), the above doses of ramiprilat or HOE 140 had significant vascular antagonism of sufficient duration against serial challenge with angiotensin I (AI) or bradykinin, respectively. After reperfusion, myocardial infarct size (IS) was determined by tetrazolium staining and expressed as a percentage of area at risk (AR). IS/AR% was significantly reduced in rabbits that received ramiprilat (20 +/- 6%, p < 0.05) as compared with those that received saline (41 +/- 6%), ramiprilat plus HOE 140 (47 +/- 2%), or HOE 140 alone (43 +/- 4%, mean +/- SEM). AR as a percentage of total LV mass was not different between any of the four treatment groups. Tachycardia was observed during early reperfusion in each group treated with ramiprilat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduction of myocardial infarct size in rabbits by ramiprilat: reversal by the bradykinin antagonist HOE 140. 768 28

The transgenic TGR(mRen-2)27 rat, in which the Ren-2 mouse renin gene is transfected into the genome of the Sprague-Dawley rat, develops severe hypertension at a young age that responds to inhibitors of angiotensin-converting enzyme and to antagonists of the type 1 angiotensin II (Ang II) receptor. Despite this evidence that the hypertension is Ang II dependent, TGR(mRen-2)27 rats have suppressed renal renin and renin mRNA content, and there is controversy concerning the plasma levels of renin and Ang II in these rats. We investigated the effect of the transgene on circulating and tissue levels of angiotensin and bradykinin peptides in 6-week-old male homozygous TGR(mRen-2)27 rats. Systolic blood pressure of TGR(mRen-2)27 rats was 212 +/- 4 mm Hg (mean +/- SEM, n = 25) compared with 108 +/- 2 mm Hg (n = 29) for age- and sex-matched Sprague-Dawley rats. Compared with control rats, TGR(mRen-2)27 rats had increased plasma levels of active renin (4.5-fold), prorenin (300-fold), and Ang II (fourfold) as well as tissue levels of Ang II (twofold to fourfold in kidney, adrenal, heart, aorta, brown adipose tissue, and lung and 18-fold in brain). Plasma angiotensinogen levels were reduced to 73% of control, and plasma aldosterone levels were increased fourfold. Plasma angiotensin-converting enzyme was reduced to 64% of control. Compared with control rats, TGR(mRen-2)27 rats had increased bradykinin levels in brown adipose tissue (1.9-fold) and lung (1.6-fold).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Angiotensin and bradykinin peptides in the TGR(mRen-2)27 rat. 759 Oct 27

1. In patients treated with angiotensin-converting enzyme inhibitors, kinin-related effects have been postulated repeatedly, but information on changes in plasma kinin levels in these patients is sparse. Difficulties in the measurement of plasma kinins account for this, at least in part. 2. The main purpose of the present study was to investigate, in normal human subjects, the effect of the angiotensin-converting enzyme inhibitor quinapril on plasma kinins. 3. High-affinity antisera (Kd < 10(-11) mol/l) of C-terminal specificity were raised in rabbits for radioimmunoassay of immunoreactive kinins activating the bradykinin B2-receptor, and three different liquid- and solid-phase extraction methods for plasma kinins were evaluated. Ethanol and subsequent petroleum ether extraction of 5-40 fmol of bradykinin added to plasma yielded recoveries of 39 +/- 16% (mean +/- SD); normal kinin levels in human plasma were 18.6 +/- 3.3 pmol/l (mean +/- SEM). Solid-phase extraction on urea-equilibrated phenylsilylsilica produced recoveries of 89 +/- 5% and normal values of 36.4 +/- 18 pmol/l. Finally, with an assay based on ethanol extraction alone, recoveries of 100 +/- 16% and normal values of 16.8 +/- 5.8 pmol/l were obtained, with a detection limit of 1.5 fmol/ml of plasma. Blanks were below the detection limit. Serial dilution of plasma extracts (n = 4) provided linear kinin concentrations (r = 0.99). For two different plasma pools, coefficients of variation for within-assay precision were 16.7% and 21.7%, respectively. Between-assay coefficients of variation were 12.8% and 17.4%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma kinins increase after angiotensin-converting enzyme inhibition in human subjects. 787 46


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