Disparate effects of insulin on isolated rabbit afferent and efferent arterioles

Despite evidence that insulin per se may be an important regulator of glomerular hemodynamics, little is known about its direct action on the glomerular afferent arterioles (Af-Art) and efferent arterioles (Ef-Art), the crucial vascular segments that control glomerular hemodynamics. In the present study, we examined the direct effect of physiological concentrations of insulin on isolated microperfused rabbit Af- and Ef-Arts. After cannulation, vessels were equilibrated in insulin-free medium for 30 min. To determine whether insulin causes vasodilation or constriction, increasing doses (5, 20, and 200 microU/ml) were added to the bath and lumen of arterioles that were either preconstricted to 50% of control diameter with norepinephrine or left nonpreconstricted. Insulin caused no vasoconstriction in either Af- or Ef-Arts, but it reversed norepinephrine-induced constriction in Ef-Arts but not Af-Arts (suggesting a vasodilator action selective to the Ef-Art): at 200 microU/ml, insulin increased Ef-Art luminal diameter by 75.8 +/- 7.0% from the preconstricted level (n = 6; P < 0.008). The vasorelaxant effect of insulin on Ef-Arts was not affected by blockade of either endothelium-derived relaxing factor/nitric oxide or prostaglandin synthesis. Despite the lack of effect of insulin on Af-Art when added after the equilibration period, when Af-Arts were equilibrated in the presence of either 20 or 200 microU/ml insulin, their basal diameter was significantly reduced (11.7 +/- 0.9 microns; P < 0.025, n = 6, and 12.0 +/- 0.9 microns; P < 0.025, n = 7, respectively) compared with nontreated Af-Arts (16.2 +/- 1.3 microns; n = 7). In conclusion, this study demonstrates that at physiological concentrations, insulin dilates NE-constricted Ef-Arts, while insulin pretreatment enhances Af-Art tone. The disparate actions of insulin on the Af- vs the Ef-Art may contribute to its beneficial effect on glomerular hypertension.     

Role of the efferent arteriole in glomerular hemodynamics of superficial nephrons

Hemodynamic pressure in glomerular capillaries (GCP) and in first order peritubular capillaries (EAP) in superficial nephrons of mutant Wistar rats with surface glomeruli was measured by micropuncture with a servo-nulling device in the following conditions: 1) control;2) norepinephrine infusion (NE); 3) epinephrine infusion (E): 4) dopamine infusion (D); 5) hemorrhagic hypotension (HH); 6) HH + NE; 7) HH + E; 8) HH + D; 9) acute hypertension secondary to bilateral cervical vagotomy and occlusion of both common carotid arteries. BP was also recorded. Both GCP/BP and EAP/GCP ratios averaged 0.40 in control conditions, but only the EAP/GCP ratio remained constant in all conditions under study, indicating that approximately 60% of the hydrostatic pressure in glomerular capillaries is constantly dissipated by the efferent arteriole. When all values of EAP were plotted against the respective values of GCP, a liner relationship was detected (r=0.843). These results indicate that changes of pressure in the first order peritubular capillaries of superficial nephrons are merely secondary to changes in glomerular capillary pressure.     

Time course of the medial olivocochlear efferent effect on otoacoustic emissions in humans

The time course of the medial olivocochlear efferent system has been studied in humans, using the suppressive effect of a contralateral broad-band noise (CBBN) on 2f1-f2 distortion product otoacoustic emissions (DPOAE) amplitude. DPOAE were recorded with F2 at 1.5 kHz, with a temporal resolution of 2.6 s, in the presence and absence of a 40 dB SL continuous CBBN, whose duration ranged between 30 s and 20 min. The CBBN suppressive effect on DPOAE amplitude was greatest from the first 2.6 s, and was sustained for 20 min. At the CBBN offset, when the CBBN duration was > or = 2 min, DPOAE amplitude continued to increase for > 1 min, showing an efferent effect outlasting CBBN stimulation.     

Three-dimensional modeling of renal glomerular capillary networks

Using whole cell patch clamp recordings on unfertilized eggs of the ascidian Ciona intestinalis, we are able to detect ryanodine receptors within the oocytes. Our approach is based on measurements of the voltage-activated inward calcium currents. Two types of Ca2+ currents have been described on the oocyte membrane of Ciona: a low threshold slowly activating current, and a high threshold faster one. We show here that caffeine induces a decrease in the intensity of the Ca2+ currents, when applied either externally or internally from the mouth of a patch pipette. Caffeine application mimics fertilization which transiently decreases the high threshold Ca2+ current density during density during the first meiotic cycle. Ryanodine (> 1 nM) has an effect similar to caffeine. This partial decrease in Ca2+ current density elicited by caffeine or ryanodine is prevented by intracellular application of the calcium chelator BAPTA, then imputable to calcium release. In summary, the depolarization-induced Ca2+ current intensity allows monitoring of an intracellular calcium store which is sensitive to low concentrations of ryanodine in Ciona oocytes. Further identification of a ryanodine receptor was obtained by immunological staining with antibodies against mammalian skeletal muscle ryanodine receptor. Ryanodine receptors were asymmetrically localized in the cortex of Ciona eggs. We discuss the methodological relevance of our patch-clamp approach, in connection with the possible biological role of such a ryanodine receptor in the early stages of development.     

Remarks on the phylogeny and structure of fatty acid binding proteins from parasitic platyhelminths

Four fatty acid binding proteins (FABPs) have been described in 4 parasitic platyhelminths: Schistosoma mansoni, Schistosoma japonicum, Fasciola hepatica and Echinococcus granulosus. FABPs form a multigenic family of cytosolic proteins widely distributed in metazoan tissues, the function of which is still poorly understood. These helminth proteins have recently received attention, since there are reports to indicate that S. mansoni and F. hepatica FABPs may be protective antigens. In addition, these proteins could play a major role in the parasites' life-cycles because platyhelminths are unable to synthesize de novo most of their lipids. We have undertaken phylogenetic and structural analyses of platyhelminth FABPs in an attempt to characterize features of biological relevance. Phylogenetically, these FABPs appear to be more closely related to those of vertebrate heart, mammary gland, muscle, retina, skin, brain and myelin, although no clear functional relationships were established between them. We describe several conserved motifs characteristic of specific groups of FABPs. Hydrophilicity, flexibility and accessibility analyses revealed several major putative epitopes for the E. granulosus FABP, EgDf1, that appear to be centred in loops of the EgDf1 3-dimensional structure modelled by molecular replacement.     

Variations in histologic and ultrastructural findings in renal glomerular biopsies

On the basis of 506 renal biopsies performed within a six-year period (237 of which were evaluated electron-microscopically) the authors discovered that in 11 cases the diagnosis based on electron microscopic examination had to be corrected or supplemented by the diagnostic statement of membranous glomerulonephritis. These cases included 1 boy (HBsAg positive), 2 men and 8 women were middle aged. 5 women were treated due to polyarthritis. All cases when examined light-microscopically yielded a pattern evaluated as normal, or as minute abnormalities of glomeruli. Half-thick sections were not sufficient for the diagnosis. 3 cases of biopsies yielded a variously developed chronic tubulointerstitial nephritis, two cases were accompanied with polyarthritis. On the basis of the latter the authors consider the electron microscopic examination as indicated: 1. in cases when the diagnosis statement is not achieved by other examinations, 2. findings are in the range of the so-called variable norm, 3. in all cases of minute abnormalities in glomeruli detected without electron microscopy, 4. the impact of any of effective drugs cannot be excluded, 5. the diagnostic conclusion based on renal biopsy and the clinical-laboratory pattern of the disease are inconsistent. The authors assume that especially the fourth and fifth groups are going to be gradually supplemented and made more precise. (Fig. 1, Ref. 5.).     

Medullary mechanism of the inhibition on renal sympathetic efferent activities by stimulation of the cervical vagal afferent nerve in rabbits

The presence of angiographic evidence of thrombus is generally thought to be a contraindication to coronary stent placement. This report describes four patients in whom angiographic thrombus was lysed using the Dispatch infusion catheter prior to coronary stenting. Urokinase was infused via the Dispatch catheter with resolution of angiographic evidence of thrombus in all cases. No complications were encountered using this technique, and all patients had excellent angiographic results after stenting. We conclude that lysis of intracoronary thrombus using the Dispatch infusion catheter is feasible and appears safe in this small study. Further trials are needed to determine if this technique reduces the acute stent thrombosis rate compared to other techniques for stent deployment in the presence of angiographic evidence of thrombus.     

Effects of smoking on renal hemodynamics in healthy volunteers and in patients with glomerular disease

Patients with renal disease who smoke have a poor renal functional prognosis, but the mechanisms involved have not been explored. In this controlled study, the effects of smoking and sham smoking were compared in 15 healthy normotensive volunteers. All were occasional smokers and abstained from smoking for 48 h as documented by urinary cotinine measurements. These data were compared with those of seven patients with biopsy-confirmed IgA glomerulonephritis, also occasional smokers. Renal clearance examinations were obtained after hydration in the supine position before and while smoking two cigarettes or sham cigarettes in random order on 2 consecutive days. GFR and effective renal plasma flow were determined using In111-diethylenetriamine penta-acetic acid and 131I-hippurate with a dual tracer infusion clearance technique. In an ancillary study with six volunteers, the effect of smoking was compared with the effect of nicotine-containing chewing gum. In healthy volunteers, sham smoking caused a minor but significant increase of mean arterial pressure (MAP) and GFR with no significant change of effective renal plasma flow, filtration fraction (FF), or renovascular resistance. Smoking caused a significant and more marked increase of MAP (from baseline 92.8+/-8.98 to 105+/-7.78 mmHg) and heart rate (from 61.7+/-7.52 to 86.4+/-9.87 min(-1)), accompanied by a significant increase in arginine vasopressin (from 1.27+/-0.72 to 19.9+/-27.2 pg/ml) and epinephrine (from 37+/-13 to 140+/-129 pg/ml). During smoking, GFR decreased in all but one volunteer (from 120+/-17.7 to 102+/-19.3 ml/min per 1.73 m2), and this was accompanied by a significant decrease of FF (from 21.3+/-4.24 to 17.4+/-3.41%) and an increase in renovascular resistance (from 97.6+/-27.2 to 108+/-30.4 mmHg x min/ml per 1.73 m2). These findings were reproduced with nicotine-containing chewing gum. In contrast, when patients with IgA glomerulonephritis smoked, a similar increment in MAP was noted, the changes of FF were not uniform, and a small but consistent increase of urinary albumin/creatinine ratio was observed. An additional 20 volunteers were subjected to the smoking arm of the study for statistical evaluation of the GFR change in patients. The difference between the change of GFR between all volunteers (n = 35) and patients (n = 7) was significant (P < 0.005). It is concluded that the known effects of smoking and nicotine on the sympathetic nervous system and on systemic hemodynamics are accompanied by significant acute changes in renal hemodynamics and albuminuria. These findings are of interest because of the known effects of smoking on progression of renal disease.     

Varieties of vascular anastomoses in the course of renal allotransplantation

The results of conduction of 305 renal transplantation operations are adduced. Ultrasonic dopplerography ought to be applied in complex of preoperational examination of potential recipient. Maximal usage of the donors kidney with atypical vascular pedicle structure is mandatory and possible. In the cases of the main line type of the vessels structure, while other equal conditions present, the end to end anastomosis formation with a. iliaca internal is preferable. The ligature of vessel above and below to the defect is a single effective method of treatment of secondary arrosive hemorrhage from a, iliaca externa.     

Evaluation of long-term follow-up of glomerular function in renal transplant recipients

The determinants and outcomes of unwanted pregnancies were explored in a prospective study of 1454 women who delivered in Moscow, Russia, during 1984-85. Mothers were interviewed during their postpartum hospital stay and again 3 years later. 131 women (9%) demonstrated a negative attitude toward their pregnancy. Another 72 women (5%) had a negative attitude initially, but developed positive feelings over the course of the pregnancy. The percentage of unwanted pregnancies was 2.9 times greater among unmarried women (14.9%) than married women (5.1%). Poor marital relationships, inadequate living conditions, tobacco/alcohol use, and low per capita income were found significantly more often among women with unwanted pregnancies. Significantly more infants of mothers with unwanted than wanted pregnancies had infants who were premature (28.3% vs. 9.5%) and low birth weight, but there was no significant difference in neonatal complications. Mothers of unwanted infants also were more likely to delay prenatal care and attend infrequently and, once the child was born, made fewer visits to the pediatrician. Even if unwanted pregnancy has no adverse medical sequelae, being unwanted should be considered a psychosocial risk factor with implications for a child's development.     

Early diagnosis of impaired glomerular and renal tubule function in patients with acromegaly

BACKGROUND: Albuminuria (A), increased urinary excretion of glycosaminoglycans (GAG) and increased activity of N-acetyl-beta-glucosaminidase (NAG) in urine are early markers of glomerular and tubular changes in various pathological conditions at a time when renal functions do not yet display impaired function and when the changes are still reversible. The objective of the presented study was to assess to what extent these early changes may play a part in acromegaly. METHODS AND RESULTS: In a group of 24 acromegalic patients and in 18 healthy controls the authors examined the microalbuminuria (RIA Immunotech Prague), urinary excretion of glycosaminoglycans (spectrophotometrically by the carbazole method) and they assessed the NAG activity in urine (spectrophotometrically). In acromegalic patients before surgical and pharmacological treatment the authors found, as compared with healthy controls, increased urinary excretion of GAG [4.4 (0.9-22.7) g/mol creat. vs. 2.1 (0.8-5.5) g/mol creat, p < or = 0.001], elevated albuminuria [3.6 (0.3-37.4) g/mol creat. vs. 0.5 (0.1-2.2) g/mol creat, p < or = 0.001 and an enhanced NAG activity [1005 (345-2935) U/l vs. 470 (195-1135) U/l, p < or = 0.001]. The parameters of albuminuria and urinary GAG excretion characterize rather glomerular renal function, they correlate mutually (r = 0.64 p < or = 0.001), while the urinary NAG activity, depending on tubular function, does not correlate with them. No correlation of these parameters with the IGI concentration (for A: 0.3, for GAG: -0.04 and for NAG: -0.02 according to Pearson was found. CONCLUSIONS: In hormonally active acromegalic patients without apparent altered renal functions (normal serum creatinine, Albustix negative) the authors detected early changes of glomerular and tubular functions. They found a significant correction between albuminuria and GAG excretion.     

The renal handling of parathyroid hormone. Role of peritubular uptake and glomerular filtration

The mechanisms of uptake of parathyroid hormone (PTH) by the kidney was studied in anesthetized dogs before and after ureteral ligation. During constant infusion of bovine PTH (b-PTH 1-84), the renal arteriovenous (A-V) difference for immunoreactive PTH (i-PTH) was 22+/-2%. After ureteral ligation and no change in renal plasma flow, A-V i-PTH fell to 15+/-1% (P < 0.01), indicating continued and significant uptake of i-PTH at peritubular sites and a lesser role of glomerular filtration (GF) in the renal uptake of i-PTH. Since, under normal conditions, minimal i-PTH appears in the final urine, the contribution of GF and subsequent tubular reabsorption was further examined in isolated perfused dog kidneys before and after inhibition of tubular reabsorption by potassium cyanide. Urinary i-PTH per 100 ml GF rose from 8+/-4 ng/min (control) to 170+/-45 ng/min after potassium cyanide. Thus, i-PTH is normally filtered and reabsorbed by the tubular cells. The physiological role of these two mechanisms of renal PTH uptake was examined by giving single injections of b-PTH 1-84 or synthetic b-PTH 1-34 in the presence of established ureteral ligation. After injection of b-PTH 1-84, renal A-V i-PTH was 20% only while biologically active intact PTH was present (15-20 min). No peritubular uptake of carboxyl terminal PTH fragments was demonstrable. In contrast, after injection of synthetic b-PTH 1-34, renal extraction of N-terminal i-PTH after ureteral ligation (which was 13.4+/-0.6% vs. 19.6+/-0.9% in controls) continued for as long as i-PTH persisted in the circulation. These studies indicate that both GF and peritubular uptake are important mechanisms for renal PTH uptake. Renal uptake of carboxyl terminal fragments of PTH is dependent exclusively upon GF and tubular reabsorption, whereas peritubular uptake can only be demonstrated for biologically active b-PTH 1-84 and synthetic b-PTH 1-34.     

Nitric oxide-20-hydroxyeicosatetraenoic acid interaction in the regulation of K+ channel activity and vascular tone in renal arterioles

The present study examined whether inhibition of P4504A enzyme activity and the formation of 20-HETE contributes to the activation of K+ channels and vasodilator effects of nitric oxide (NO) in renal arterioles. Addition of an NO donor to the P4504A2 enzyme that produces 20-HETE increased visible light absorbance at 440 nm indicating that NO binds to heme in this enzyme. NO donors also dose-dependently inhibited the formation of 20-HETE in microsomes prepared from renal arterioles. In patch-clamp experiments, NO donors increased the open-state probability of a voltage-sensitive, large-conductance (195+/-9 pS) K+ channel recorded with cell-attached patches on renal arteriolar smooth muscle cells. Blockade of guanylyl cyclase with [1H-[1,2,4]Oxadiazolo[4,3-a] quinoxalin-1-one] (ODQ, 10 micromol/L), or cGMP-dependent kinase with 8R,9S,11S-(-)-9-methoxycarbamyl-8-methyl-2,3,9,10-tetrahydro-8, 11-epoxy-1H,8H,11H-2,7b,11a-trizadibenzo-(a,g)-cy-cloocta-(c ,d, e)-trinden-1-one (KT-5823) (1 micromol/L) did not alter the effects of NO on this channel. In contrast, inhibition of the formation of 20-HETE with 17-octadecynoic acid (1 micromol/L) activated this channel and masked the response to NO. Preventing the NO-induced reduction in intracellular 20-HETE levels also blocked the effects of NO on this channel. Sodium nitroprusside (SNP) increased the diameter of renal interlobular arteries preconstricted with phenylephrine to 80+/-4% of control. Blockade of guanylyl cyclase with ODQ (10 micromol/L) attenuated the response to SNP by 26+/-2%; however, fixing 20-HETE levels at 100 nmol/L reduced the response by 67+/-8%. Blockade of both pathways eliminated the response to SNP. These results indicate that inhibition of the formation of 20-HETE contributes to the activation of K+ channels and the vasodilator effects of NO in the renal microcirculation.     

Effects of adrenomedullin on rat cerebral arterioles

The effects of adrenomedullin on isolated rat intracerebral arterioles were investigated and compared with those of calcitonin gene-related peptide (CGRP) and amylin. Adrenomedullin produced dose-dependent vasodilation (maximum dilation 27.1 +/- 2.1% at 3 x 10(-7) M, median effective dose (EC50)) 1.6 x 10(-9) M). CGRP produced similar vasodilation (19.8 +/- 4.1%) at 10(-7) M with a lower EC50 of 2.8 x 10(-11) M. Amylin did not cause vasodilation at concentrations up to 10(-6) M. Adrenomedullin-induced vasodilation was significantly suppressed by CGRP-(8-37). These data suggest that adrenomedullin is a potent vasodilator for arterioles in the cerebral microcirculation that acts through CGRP receptors.     

Low dose angiotensin converting enzyme inhibition and glomerular permselectivity in renal transplant recipients

In this study, we determined the fractional clearance of neutral polydisperse dextrans (theta D) and monodisperse dextran sulfate (theta DS) to describe glomerular size and charge selectivity in 25 renal transplant recipients with proteinuria. Thirteen were treated with low dose lisinopril for six months (group 1) and 12 patients without ACE inhibitor therapy formed group 2. Mean arterial blood pressure was stable (group 1, 112 +/- 4; group 2, 109 +/- 2 mm Hg at baseline and after 6 months) whereas creatinine clearance, glomerular filtration rate and renal plasma flow decreased nonsignificantly but were comparable at any time. Lisinopril treatment lowered filtration fraction (22 +/- 2 vs. 19 +/- 2%, P = 0.07) whereas no change was seen in group 2 (20 +/- 2%). The fractional protein excretion (mg urinary protein per day/ml creatinine clearance per day) was stable in group 1, but significantly increased in group 2. The same pattern was found for theta D larger than 56 A. theta DS was stable and consistently elevated in both groups at any time. We conclude that low dose ACE inhibitor treatment in proteinuric renal transplant recipients stabilizes glomerular size selectivity independently of its systemic hemodynamic effects.