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.     

Functional and morphologic studies on allogeneic venous transplants

Erythropoietin production was studied in 30-day-old and adult rats previously injected with pharmacological doses of isoproterenol. The animals were stimulated either by hypobaric hypoxia or by a combination of hypoxia and acute anemia. The erythropoietic activity of the plasma was measured by 59Fe incorporation in total circulating red blood cells of mice made polycythemic by chronic hypoxia. The results were converted to units of erythropoietin (IRP). A significant reduction of erythropoietin production was observed only in young rats. Our interpretation of the findings is that isoproterenol induced the differentiation of the salivary glands in the young animals hence reducing hormone production at the extrarenal (submandibular) level.     

Impact of cyclo-oxygenase blockade on juxtamedullary microvascular responses to angiotensin II in rat kidney

1. Experiments were designed to evaluate the hypothesis that cyclo-oxygenase products modulate the influence of angiotensin II (AII) on the renal juxtamedullary microvasculature of enalaprilat-treated rats. 2. The in vitro blood-perfused juxtamedullary nephron technique was utilized to provide access to afferent arterioles, efferent arterioles and descending vasa recta located in the outer stripe of the outer medulla. 3. Baseline afferent arteriolar diameter was 20.8 +/- 1.9 microns in kidneys subjected to cyclo-oxygenase blockade (1 mumol/L piroxicam), a value significantly lower than that observed in untreated kidneys (26.1 +/- 1.0 microns). Baseline diameters of efferent arterioles and outer medullary descending vasa recta did not differ between untreated and piroxicam-treated groups. 4. Topical application of 1 nmol/L AII reduced blood flow through outer medullary descending vasa recta by 22 +/- 6% in untreated kidneys and by 24 +/- 7% in piroxicam-treated kidneys. 5. In untreated kidneys, AII (0.01-100 nmol/L) produced concentration-dependent afferent and efferent arteriolar constrictor responses of similar magnitudes. Neither afferent nor efferent arteriolar AII responsiveness was significantly altered in piroxicam-treated kidneys, although afferent responses exceeded efferent responses at AII concentrations > or = 10 nmol/L. 6. We conclude that endogenous cyclo-oxygenase products exert a vasodilator influence on juxtamedullary afferent arterioles under baseline conditions. Although cyclo-oxygenase inhibition had little effect on juxtamedullary microvascular responses to AII, the response to high AII concentrations may be modulated by cyclo-oxygenase products in a manner which delicately alters the relative influence of the peptide on pre- vs postglomerular resistances.     

Functional maturation of the somatosensory neocortex S1 in the rat. Electrophysiological and histochemical study (author's transl)

The functional maturation of the somatosensory neocortex has been studied using the projection areas of the whiskers. Natural stimulation of the whiskers evokes global potentials and unitary responses from the 4th postnatal day on. From the 2nd postnatal week the characteristics of the unit responses approximate in latency, topographic organisation of the projections, coding of the directions and temporal characteristics of the stimulation those of the adult. The histochemical activity of succinyl dehydrogenase is demonstrated in layer IV a little before the first electrophysiological response but the typical massed organisation is only seen from the 5th postnatal day. During maturation optical densitometry shows a rapid rise in enzyme activity untill the 7th postnatal day then a slower rise up to the 21st day after which it stabilises.     

Adaptive changes of juxtamedullary glomerular filtration in the remnant kidney

The participation of surviving juxtamedullary nephrons in the adaptive changes of glomerular filtration that occur in response to loss of functioning nephron mass was examined by direct micropuncture of the rat renal papilla. The solitary remnant kidney (RK) in rats with an 85% reduction of renal mass demonstrated strikingly elevated values for single nephron glomerular filtration rate (SNGFR) in both superficial (46.1 +/- 3.2 nl/min) and juxtamedullary (73.5 +/- 6.1 nl/min) nephrons in comparison to respective values observed in normal hydrophenic rats (superficial SNGFR = 15.0 +/- 1.9 nl/min, P less than 0.001, and juxtamedullary SNGFR = 30.2 +/- 3.2 nl/min, P less than 0.001). In RK rats, the proximal portions of both superficial and juxtamedullary nephrons exhibited a marked increase in absolute fluid reabsorption as well as a markedly enhanced delivery of fluid to more distal portions of the nephron. These observations indicate that similar, not preferential, functional adaptations in glomerular filtration occur concomitantly in both superficial and juxtamedullary nephrons consequent to reduction of renal mass.     

Functional and morphologic changes after combined maxillary intrusion and mandibular advancement surgery

PURPOSE: The purposes of this investigation were 1) to compare the morphology and function of patients with combined vertical maxillary excess (VME) and mandibular retrognathia with that of controls, and 2) to examine how these parameters change after combined maxillary intrusion and mandibular advancement surgery. PATIENTS AND METHODS: Fifteen female VME/retrognathic patients were compared with 26 female controls before and for up to 3 years after orthognathic surgery. Facial skeletal morphology, mandibular range of motion, maximum isometric bite force, and levels of electromyographic activity (EMG) in selected muscles of mastication were measured on all subjects. Where appropriate, one-way analysis of variance (ANOVA) or t-tests were used to compare the patients with controls. Univariate repeated-measures ANOVA was used to study longitudinal changes. RESULTS: Preoperatively, patients' morphologic measurements were characteristic of VME compounded by mandibular retrognathia. At surgery, the maxilla was elevated an average of 2.8 mm, and the mandible was lengthened by an average of 7.1 mm. All of the postoperative morphologic measurements were closer to normal values. The patients' masseter mechanical advantage was significantly lower than that of controls both before and after surgery. Surgically induced changes in mechanical advantage were very small. The patients' maximum range of motion and excursion during mastication were all lower than those of controls before surgery. All measurements of mobility decreased immediately after surgery, with a gradual return to preoperative values. However, even 3 years after surgery, all of the motion measurements remained smaller than those of the controls. Before surgery, the patients had maximum isometric bite forces significantly lower than those of controls. Bite forces increased significantly after surgery, approaching normal values within 2 years. The activity levels in the muscles of mastication during isometric bites were not significantly altered by surgery. CONCLUSIONS: This study confirms that VME/retrognathia patients suffer from substantial deficiencies in their oromotor function. Surgical correction of this particular type of dentofacial deformity improves both the morphologic and functional deficits. Although some changes were not statistically significant, all were toward normalization of the presurgical values.     

Functional maturation of cochlear active mechanisms and of the medial olivocochlear system in humans

The aim of this study was to investigate the functional development of cochlear active mechanisms and of the medial efferent olivocochlear system. Otoacoustic emissions (evoked and spontaneous) were recorded in 42 preterm neonates (conceptional age ranging form 33 to 39 weeks) and a control group of 20 young normal-hearing adults. Medial olivocochlear system activity was examined by coupling evoked otoacoustic emission recording to a contralateral stimulation. Otoacoustic emission recordings were carried out using the Otodynamic ILO88 software and hardware. The stimuli were unfiltered clicks and the contralateral stimulation was broad band noise of 50 and 70 dBSPL delivered by an Adam generator. The results revealed the presence of EOAEs and SOAEs from at least 33 weeks in humans, suggesting that the functional maturation of the outer hair cells is nearly complete at that age. The study further revealed that the contralateral stimulation had no effect on evoked otoacoustic emissions in preterm neonates. The lack of activity observed in medial olivocochlear system indicated functional immaturity here, at least before full-term birth.     

Ruffle-ended maturation ameloblasts in the pigmentation zone of rat incisor

Rats were perfused with glutaraldehyde and the incisors were dissected free. Midsagittal slice of the incisor were demineralized and the pigmented zone were further sliced into thin cross sections. The lysosomal activity was demonstrated utilizing CMPase. Two patterns of localization were observed. Weak local reaction product associated with the pigment granules. The second one was intense reaction product with some of the ruffled border of ameloblasts. A suggested role for these localizations were discussed in relation to pigment release into the enamel surface.     

Postnatal maturation of renal cortical peritubular fibroblasts in the rat

Differences in Minnesota Multiphasic Personality Inventory-2 (MMPI-2) response latencies between groups instructed to respond honestly or fake were explored. There were 120 undergraduate students who completed a computer administered MMPI-2 with instructions to either respond honestly, to underreport psychopathology, or to overreport psychopathology. Results showed that subjects required significantly more time to respond in a manner that was inconsistent with their response set when pattern of endorsement (acceptance vs. rejection) was considered and less time when pattern of endorsement was not considered. The differential response of subjects across groups suggests that response latencies are related to response styles and that future research may indicate a methodology for utilizing response latencies in assessing response validity.     

Functional and morphologic characterization of thoracic aorta in heritable hyperlipidemic Yoshida rats of different ages

We investigated serum and aortic tissue lipid content, in vitro aortic response to drugs, and morphology of thoracic aorta in Pittsburgh Yoshida rats (YOS), a new animal model of endogenous hyperlipidemia. Experiments were performed on 2-, 6-, and 18-month-old rats. Normolipidemic Brown Norway rats (BN) were used as controls. Both serum cholesterol and triglycerides increased significantly with age in YOS rats, but remained constantly low in the control group. In YOS rats, absolute serum concentration of high density lipoprotein (HDL)-cholesterol increased significantly with age, although HDL-cholesterol/total-cholesterol ratio decreased. In contrast, no difference in cholesterol content in aortic tissue was detected between the two animal strains or among different age groups. The contractile force generation of thoracic aorta to norepinephrine (NE) and serotonin increased with age in both strains of animals. The endothelium-dependent relaxation induced by acetylcholine (ACh) was significantly reduced in 6- and 18-month-old YOS as compared with 2-month-old YOS but not in BN. ATP-induced relaxation was significantly impaired in YOS thoracic aorta. In contrast, the relaxation induced by NaNO2 acting in smooth muscle did not vary with age in either YOS or BN. Only alterations in endothelial cells, not typical atheromatous injuries in thoracic aorta wall were detected in YOS even at age 18 months. Our data indicate that despite high serum lipid levels, YOS do not develop typical atheromatous lesions or functional and morphologic damage of smooth muscle cells in thoracic aorta, whereas YOS show decreased endothelium-dependent relaxation and morphologic alteration of endothelial cells.     

Effect of maturation and aging on material and ultrasonographic properties of equine superficial digital flexor tendon

Results of studies in human beings and other species have indicated that aging significantly influences the strength, modulus of elasticity, and energy storage ability of tendon. We wanted to determine the effects of aging on the material and ultrasonographic properties of equine superficial digital flexor (SDF) tendon. Ultrasonographic measurements of left forelimb SDF tendon cross-sectional area and mean echogenicity were made in 23 standing horses ranging in age from 2 to 23 years. All horses had not been in work for a minimum of 6 months prior to the study. After euthanasia, left forelimb bone-muscle-tendon-bone specimens were mounted in a materials testing system. The SDF tendon was cyclically loaded sinusoidally 100 times at 0.5 Hz from 1.5 to 5.0% strain, then was submitted to 10-minute creep-and-stress relaxation tests. Modulus of elasticity, load at 3% strain, and creep-and-stress relaxation were determined for each specimen. A significant positive correlation was found between elastic modulus and age. Correlation was not found between age and SDF tendon cross-sectional area or mean echogenicity. When 2-year-old horses were compared with older horses, the latter had tendons with a significantly (P = 0.007) greater modulus of elasticity. The authors conclude that increasing age through maturity is associated with a corresponding increase in equine SDF tendon elastic modulus.     

Development of the hypothalamic vasopressin system and nephrons in Meriones shawi during ontogenesis

This study has evaluated the development of the hypothalamic vasopressin system and nephrons of the kidney in desert rodents, Meriones shawi, which effectively retain water by excretion of highly concentrated urine. The vasopressin system was studied immunocytochemically at the 18th fetal day, at the 2nd, 13th, 27th postnatal days and in adulthood. The kidneys were investigated at the 2nd, 13th postnatal days and in adulthood using microdissection technique. Occasional vasopressin-immunoreactive neurons were observed as early as the 18th fetal day, only in the paraventricular nucleus. From the 2nd postnatal day onwards, vasopressin neurons increased progressively in number, being mainly concentrated in the supraoptic and paraventricular nuclei, as well as in the ventral retrochiasmatic region. Transient neuronal populations were also observed at the 13th postnatal day in the lateral preoptic area and anterior hypothalamic nucleus. Apart from the neurons, the glandular cells of the tuberal lobe showed immunostaining from the 18th fetal day, the first age studied, until the 13th postnatal day. The fibers of differentiating vasopressin neurons grew towards the circumventricular/neurohemal organs, terminating in the organum vasculosum of the lamina terminalis and the lateral ventricles as early as the 18th fetal day, as well as the third ventricle, the posterior lobe and the external zone of the median eminence between the 2nd and 13th postnatal days. The kidney in 2-day-old Meriones comprised nephrons at different stages of development from an S-shaped body to well-differentiated nephrons. At the 13th postnatal day, as in adulthood, the nephrons were well differentiated and characterized by long, thin loops descending to different levels of papilla. Thus, according to our morphological data the hypothalamic vasopressin neurons and nephrons in the kidney of Meriones reach the definitive state by the end of the 2nd postnatal week.     

Glucocorticoids stimulate the maturation of H,K-ATPase in the infant rat stomach

The development of gastric H,K-ATPase from fetal to adult life was studied in the rat. The alpha and beta H,K-ATPase mRNA abundance, the protein abundance, and the enzyme activity increased postnatally. The sharpest increase in mRNA and enzyme activity was observed in the weaning period. Several intestinal enzymes are known to be stimulated by glucocorticoids at the time of weaning. To study the role of glucocorticoids in the maturation of gastric H,K-ATPase, we treated 10-d-old rats with a single injection of betamethasone. Twenty-four hours after betamethasone injection, the enzyme activity was significantly higher than in the control animals (2.6-fold, p < 0.05). The abundance of catalytic alpha H,K-ATPase protein was also increased (2.5-fold, p < 0.01). The time-dependent effect of betamethasone on alpha H,K-ATPase mRNA was determined from 6 to 24 h after treatment. Glucocorticoids did not significantly alter the mRNA abundance within 18 h. Twenty-four hours after injection, the gastric H,K-ATPase mRNA was significantly increased compared with controls (2.8- and 2.2-fold increase for alpha and beta subunits, respectively, P < 0.01 for both). In conclusion this study indicates that glucocorticoids may regulate the long-term maturation of gastric H,K-ATPase by indirectly stimulating enzyme synthesis.     

Functional transplantation of the rat pituitary gland

OBJECTIVE: These studies evaluated the ability of transplanted pituitary cells to restore pituitary function in hypophysectomized rats. METHODS: The pituitary glands of neonatal Lewis rats were rapidly removed, enzymatically dispersed, and stereotactically introduced into the third ventricle of hypophysectomized adult male Lewis rats. Four weeks after implantation, plasma levels of anterior pituitary hormones in implanted animals were compared with those of sham-transplanted control animals. RESULTS: Plasma levels of prolactin, growth hormone, thyroid-stimulating hormone, and beta-endorphin were below the range of detection in 14 sham-operated animals. In implanted animals, restitution of serum prolactin occurred in 100% of the animals tested, with levels of 2.6 +/- 1.0 ng/ml (mean +/- standard error of the mean; normal, 2-4 ng/ml). Growth hormone was assayable in 71% of the animals, with a mean value of 29 +/- 13 ng/ml over all animals (normal, 1-100 ng/ml); thyroid-stimulating hormone was restored in 68%, with mean resting levels of 79 +/- 13 ng/ml (normal, 100-400 ng/ml); luteinizing hormone levels were found in 53%, with mean levels over all animals of 0.2 +/- 0.1 ng/ml (normal, 0.5-1.0 ng/ml); and beta-endorphin was restored in 45% to high resting levels of 163 +/- 31 pg/ml (normal, 20-30 pg/ml). A challenge with hypothalamic releasing factor and a cold stress test were performed on the animals that had received transplants. Positive hormone responses to both of these tests suggested sensitivity of the pituitary grafts to both endogenous and exogenous sources of stimulation. Histological sections of paraformaldehyde-fixed brains from implanted animals clearly demonstrated survival of clusters of grafted pituitary cells. Positive immunohistochemical staining for adrenocorticotropic hormone and thyroid-stimulating hormone was demonstrated in sections of the grafted tissue. CONCLUSION: These data suggest survival of neonatal pituitary transplants in the third ventricle of adult hypophysectomized rats with concomitant restoration of anterior pituitary hormone function.     

Corticosterone has independent effects on tissue maturation and growth in the suckling rat

Glucocorticoids are associated with reduced weight gain when used to improve pulmonary function in premature infants. However, tissue maturation is stimulated during normal development by an increase in serum glucocorticoids. We evaluated the effects of glucocorticoid treatment on tissue weight gain and the activity of specific enzymes in the suckling rat, with the hypothesis that these processes are independently regulated. Before the ontogenic surge in corticosterone, 6-d-old rat pups were implanted with a pellet to release corticosterone continuously at 0 (placebo), 48, 120, 240, or 360 micro g/d. We killed the pups at 7, 9, or 12 d of age and measured tissue weights and activities of sucrase and glutamine synthetase. Serum corticosterone concentrations were elevated with dose. Tissue weight gain was proportional to ln(e) serum corticosterone at all ages. In contrast, enzyme indices of tissue maturation did not respond to corticosterone until d9. Also, intestinal tissue was more sensitive than muscle to the effects of corticosterone on weight but less sensitive to its effects on maturation. We conclude that the immediate response, in terms of weight versus the delayed response of the enzymes and their reciprocal sensitivity in muscle and gut, indicates that these processes are independently regulated.     

Appearance and maturation of T-cell subsets during rat thymus ontogeny

This study measured the release of glutamate (Glu) and aspartate (Asp) amino acid transmitters in the ventrocaudal compartment of the rat periaqueductal gray (PAG) following exposure to unilateral peripheral inflammation. The release of endogenous Glu and Asp from the rat ventrocaudal PAG was monitored with the microdialysis technique in unanesthetized, unrestrained rats. There was significant increase (1,300%) in the basal concentrations of Glu release in the 7 days Complete Freund's Adjuvant (CFA) treated group compared to 24 h mineral oil control group. Amino acid release was induced by infusing veratridine (75 microM, a sodium channel activator) directly through the 1 mm long dialysis probe. Perfusion of veratridine into the ventrocaudal PAG resulted in significant elevation of Glu and Asp amino acids. In the 24 h and 7 days CFA treated rats, veratridine-evoked release of Glu was significantly decreased in the lateral ventrocaudal PAG compared to control rats injected with mineral oil (CFA vehicle). The peak minus baseline concentrations of Glu in 24 h and 7 days CFA treated groups decreased 55.7% and 43.9%, respectively. In contrast, The basal and the peak minus baseline concentrations of Asp showed no significant change between control group and 24 h and 7 days CFA treated animals. The results provide direct evidence that Glu excitatory amino acid may be involved in nociception/nociception modulation pathway in the ventrocaudal PAG.     

Functional development of the neonatal rat retinotectal pathway

Electrophysiological activity in the neonatal rat superior colliculus was recorded to measure neuronal and synaptic activity, and, therefore, functional development. Neonatal rat pups were studied from five days to two weeks of age. The earliest activity in the superior colliculus were spontaneous discharges at a frequency of one unit per animal on postnatal day 6 (P6). Spontaneously discharging units were more numerous at P8, and the number peaked on P10. The first clear response to optic nerve stimulation was seen on P10, with relatively long and variable latencies. By P14, electrically evoked responses had much shorter latencies. The results are in line with the first response to light flash in the superior colliculus at P12/13. The evidence suggests that functional development of the rat retinotectal pathway begins at the end of the first week after birth, and that much of the functional maturation occurs mainly during the second week after birth.     

Low-affinity kainate receptors and long-lasting depression of NMDA-receptor-mediated currents in rat superficial dorsal horn

In an in vitro spinal cord slice preparation whole cell electrophysiological recordings of rat superficial dorsal horn neurons responding differentially to glutamate (Glu) and N-methyl-D-aspartate (NMDA) were investigated systematically for the role of kainate (KA) receptors in modulating their activity. In these neurons, coapplication of Glu and NMDA, as well as application of Glu immediately before NMDA, induced long- and short-lasting depressions of NMDA-induced currents as well as depression of NMDA-receptor-mediated excitatory postsynaptic currents. KA applied before NMDA mimicked Glu-induced attenuating effects. Furthermore, the low-affinity KA receptor antagonist 5-nitro-6,7,8,9- tetrahydrobenzo[G]indole-2,3-dione-3-oxime potentiated Glu-induced NMDA-receptor-mediated currents in neurons responding differentially to Glu and NMDA. These results provide evidence for a novel mechanism, which may relate to classical long-term depression, involving low-affinity KA receptors in long-lasting modulation of NMDA-receptor-mediated currents. This implies a physiological role of KA receptors in long-term modulation of sensory transmission in the superficial dorsal horn of rat spinal cord.