The mechanism of cyclosporine A (CyA) nephrotoxicity is unclear. In order to evaluate renal microcirculation seven euvolemic Munich-Wistar (MW) rats were studied after acute CyA treatment (50 mg/kg, i.v.). Both total glomerular filtration rate (GFR, 0.96 +/- 0.04 vs. 0.47 +/- 0.07 ml/min) and single nephron GFR (27.90 +/- 3.39 vs. 14.02 +/- 3.49 nl/min) declined significantly (P less than 0.001). It was observed an increase in afferent (RA, increases 188%) and efferent (RE, increases 360%) arteriolar resistances that caused a decrease on glomerular plasma flow rate (QA) from 100.99 +/- 17.09 to 44.37 +/- 13.37 nl/min (P less than 0.001). Mean glomerular capillary hydraulic pressure (PGC) increased from 45 +/- 1 to 55 +/- 4 mm Hg (P less than 0.05) and the glomerular ultrafiltration coefficient (Kf) decreased by 70% (0.096 +/- 0.030 to 0.031 +/- 0.010 nl/sec X mm Hg, P less than 0.05). Additionally, in order to study hormonal participation in this nephrotoxicity, other three groups of MW rats were previously treated with captopril (2 mg/kg, i.v.), verapamil (20 micrograms/kg/min, i.v.) or indomethacin (2 mg/kg, i.v.). Both captopril and verapamil minimized the renal effects of CyA, with a decline of approximately 25% instead of approximately 50% on GFR and RPF. Moreover, two groups of Brattleboro rats were studied. Acute CyA administration in homozygote Brattleboro rats produced a decline of only approximately 22% and approximately 31%, respectively, in GFR and renal plasma flow (RPF), when compared with MW rats (P less than 0.05). Similar results were observed in heterozygote Brattleboro rats when compared with MW rats, disclosing differences due to a different strain of rats.(ABSTRACT TRUNCATED AT 250 WORDS)
SUMMARY Plasma levels of kininogen, kallikrein, and prekalllkrein were determined in patients with malignant hypertension (MH) and compared to nonnotensive controls (NC) and patients with mild to moderate essential hypertension (EH). Also, a recently described kinin potentiating factor (KPF) was estimated by dividing the value of kininogen determined by trypsln (Kgn-Try) by that of kininogen determined by human urinary kallikrein (Kgn-HuUK). No significant alterations were detected among plasma values of prekallikrein and kallikrein of MH as compared to NC. However, Kgn-HuUK values were significantly lower in MH (1.9 ± OJ MgLBK/ml) as compared to EH and NC (2.7 ± 0.1 MgLBK/ml and 3.0 ± 0.2 MgLBK/ml respectively,p < 0.05). Furthermore, KPF values were also low (p < 0.05) in MH (1.6 ± 03) when compared with similar values obtained in EH and NC (3.0 ± 0.2 and 2.8 ± 0.1, respectively). Adequate control of blood pressure levels for 90 days in MH group caused no significant alterations in plasma levels of kininogen and KPF. It is suggested that diminished kininogen levels as well as a decrease in a kinin potentiation KPF that is generated in plasma by trypsln may be involved in the patbogenesis of human malignant hypertension. which several humoral alterations ofvasopressor systems like renin-angiotensin system, 1 catecholamines,* and more recently vasopressin 8 have been implicated in the pathogenesis of the vascular lesion. The kallikrein-kinin system has been implicated in several hypertensive states, since kinins are vasodilators 4 and also influence water and electrolyte excretion.8 -• A defective kallikrein-kinin system has been recently suggested in malignant, but not benign, hypertension in the rat.'In the present work we evaluated the levels of some plasma precursors of kallikrein-kinin system in malignant hypertension, compared to "benign" hypertension and normal subjects, by studying plasma levels of kininogen, kallikrein, and prekallikrein. Also, a newly described kinin potentiating factor* was estimated in these subjects since it is known that several potentiating substances of both exogenous' 110 or endogenous origin 11 ' " may influence the activity of the kallikrein-kinin system.
Retinol-binding protein (RBP) is a low-molecular-mass protein (21 kDa), easily filtered in renal glomeruli and very efficiently reabsorbed by the proximal convoluted tubules (PCTs). In PCT dysfunction, high concentrations of RBP are found in urine. Several methods have been used to determine RBP in serum or urine. We describe the production, selection, labeling, and utilization of anti-RBP monoclonal antibodies in two- or one-step immunoenzymometric assays for the determination of RBP. The one-step assay has good precision, with within-run and between-run CVs < 6.6% and 5.9%, respectively. Comparison with radial immunodiffusion (x) showed good agreement: y = 0.068 mg/L + 0.899x (n = 24). Comparison between the one-step (y) and two-step (x) versions of the assay also showed a very good correlation: y = 212 micrograms/L + 0.910x. The one-step assay has been adopted for routine work; it detects transthyretin-bound as well as free RBP and may have clinical usefulness in evaluating the functional status of PCTs.
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