Lithium secretion in kidneys of amphibians and reptiles under hydrated conditions

Renal lithium transport was studied at different hydration levels in five species of anuran amphibians (Bufo bufo, B. danatensis, B. viridis, Rana ridibunda, and R. temporaria), two species of urodeles (Triturus vulgaris and T. cristatus) and four species of reptiles (lizards Eremias multiocellata, Lacerta vivipara, Trapelus sanguinolentus, and Teratoscincus scincus). Under dehydration conditions, Li+ was reabsorbed in the kidneys of amphibians ans reptiles, but to a lesser degree than in mammalian kidneys: the ratio of lithium clearance (CLi) to glomerular filtration rate (GFR)--fractional lithium excretion--in dehydrated animals was in the range 0.5-0.8. The transition to the hydrated state resulted in a cessation of net renal lithium reabsorption. Under condition of high hydration, all the animals studied, except for urodeles, showed net renal secretion of Li+, i.e., CLi exceeded GFR. The ratio CLi/GFR was 1.2-1.3 in hydrated anurans and 1.7-2.3 in hydrated lizards. In urodeles, this ratio was approximately unity. It is suggested that renal lithium secretion in hydrated amphibians and reptiles reflects fluid secretion in the proximal tubule, which is additional to the glomerular filtration mechanism of fluid delivery to nephron under water loading.     

Mechanisms of secretion of toxic organic anions in mammalian kidneys

This short review considers the mechanisms of organic anion secretion in renal proximal tubules. Particular attention is given to the energy coupling of p-aminohippurate transport to inorganic anion gradients generated across both basolateral and brush-border membranes. The coupling is considered to be a consequence of the combined operation of the co-transport and anion-exchange mechanisms. A possible coexistence of several organic anion pathways with overlapping substrate specificity and/or energetic dependence of the total ion gradient are suggested. The problem of identification of transporters involved in organic anion secretion is discussed.     

Mechanism of arginine vasopressin suppression of ovine fetal lung fluid secretion: lack of V2-receptor effect

For about a quarter of a century, concerns have been expressed about published biomedical research. It became more acute after some published research and broad dissemination was found fraudulent. With the emphasis now being placed on scientifically validated or evidence-based practice, it has become more imperative that clinical guidelines be based on credible information in our textbooks and research literature. Since the early 1990s, it has been found that much of the research in our electronic databases does not meet quality standards and often is irrelevant, calling into questions problems with peer review, including the selection and publication process of our journals. This column is devoted to calling attention to these problems not only to CRNAs and other researchers, but also to the consumers of research who often use it to make changes in their practice. It also calls attention to the CRNA community about the movement toward calls for greater accountability in practice, both as to quality and cost, from which the movement toward evidence-based practice, the identification and benchmarking of best practices, and the development and implementation of clinical practice guideline has evolved. To feel ownership in anesthesia-related clinical practice guidelines, CRNAs must become involved in their development and implementation.     

Modulation of glomerular hypertension defines susceptibility to progressive glomerular injury

The fawn-hooded rat constitutes a spontaneous model for chronic renal failure with early systemic and glomerular hypertension, proteinuria (UpV) and high susceptibility to development of focal and segmental glomerular sclerosis (FGS). It has been argued that uninephrectomy (UNX) accelerates the development of glomerular injury by aggravation of glomerular hypertension and by an independent effect to promote glomerular enlargement. The present study was performed to further delineate the importance of these parameters for the development of FGS. At the age of eight weeks male rats were UNX and randomly assigned to either control (CON), enalapril (ENA) or Nw-nitro L-arginine methyl ester (NAME) treatment. In all groups glomerular hemodynamic studies were performed four weeks post-UNX. Systemic blood pressure and UpV were monitored for 4 to 12 weeks post-UNX. Kidneys were then prepared for morphologic study. ENA treatment achieved control of both systemic and glomerular hypertension, maintenance of glomerular hyperfiltration and hyperperfusion, increased ultrafiltration coefficient(Kf), and long-term protection against UpV and FGS. NAME rats showed aggravation of both systemic and glomerular hypertension, decreased renal perfusion and filtration with reduced Kf, and high filtration fraction. The incidence of FGS in NAME and CON groups was similar at 8 and 12 weeks post-UNX, respectively. Glomerular enlargement was present in CON and ENA rats, but did not correlate with injury, while glomerular tuft size was lowest in NAME rats, which displayed prominent glomerular injury. Systemic blood pressure correlated strongly with glomerular capillary pressure. We conclude that systemic and glomerular hypertension govern the development of UpV and FGS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of histamine on intestinal fluid secretion in the dog

Intra-arterial infusion of histamine into the small intestine caused about a onefold increase of blood flow, edema of the intestinal tissues and mesentery, and produced a copious secretion of fluid. The jejunal secretions had an ionic composition similar to that of plasma, whereas ileal secretions contained high concentrations of HCO3 with relative low concentrations of Cl. The secretions contained protein (1.5 +/- .2 g/100 ml, range 0.5-2.4) with a similar electrophoretic pattern of plasma protein. When lissamine green was present in the blood, it also appeared in the secretion to a considerable concentration. It is inferred from these findings that a major mechanism of fluid secretion by the action of histamine involves a filtration process across the mucosal epithelium by the incrreased tissue fluid pressure due to extensive capillary leak.     

Serum and intestinal fluid immunoglobulins and jejunal IgA secretion in Crohn's disease

Immunoglobulins in serum and proximal intestinal fluids and secretion of IgA by cultured jejunal mucosa were measured in 12 healthy subjects and 36 patients with Crohn's disease. Concentrations of IgA, IgG, IgM, and IgE in serum and intestinal fluids were similar in the two groups, except for increased serum IgA concentrations in the patients. Elevation of IgA and chronicity of disease were correlated, which suggests that the IgA alteration was a response to duration of disease rather than a primary pathogenetic factor. IgA secretion by cultured jejunum was similar in control and patient groups. Thus, no evidence was found that abnormalities of secretory immunoglobulins are pathogenetically involved in Crohn's disease.     

Mechanism of production of intestinal secretion by elevated venous pressure

A study was carried out to elucidate the physiological mechanisms responsible for the intestinal secretion produced by venous pressure elevation. In dogs, measurements were made of the rate and composition of small intestinal secretion, rate of flow and composition of intestinal lymph, plasma composition, and mucosal water content, all in response to elevations of intestinal venous pressure. Venous pressure elevations above a threshold value of 30-35 cm H2O produce secretion at a rate of approximately proportional to the value of the pressure minus the threshold value. Above the threshold value, there were large increases in the rates of lymph flow and net sustained transcapillary filtration. These rates were also roughly proportional to the incremental venous pressure. It is concluded that intestinal secretion produced by elevated venous pressure is almost surely secretory filtration, a passive process with the driving force for secretion an increase in mucosal tissue fluid pressures to values of only some 4-6 cm H2O. The increased tissue fluid pressure not only provides the driving force but also produces an increase in the hydraulic permeability of the epithelium without which the driving force would be ineffective. The transepithelial channels are large enough to permit insulin to pass freely and even plasma protein to pass in large amounts, and hence are most probably intercellular. Secretory filtration probably represents a general pathophysiological response of transporting epithelia to elevated tissue fluid pressure. It is proposed that the threshold value for secretion and associated changes is explained by dilution of the tissue fluid protein colloid osmotic pressure in a small subepithelial, juxtacapillary compartment.     

Mechanism of production of intestinal secretion by negative luminal pressure

The relationships between luminal hydrostatic pressure and fluid transport by dog jejunum in vivo studied as a sheet in the Wells clamp were compared with quantitative predictions from a model proposed for the mechanism of the secretion produced by elevated venous pressure. According to the model, the secretion produced by increasing venous pressure and the secretion produced by negative luminal pressure are both passive filtrates contingent on a transepithelial pressure of a few centimeters of H2O. We consider that the agreement between the observed and predicted responses to luminal pressure provides strong support for the model. In particular, a) the observations displayed a predicted gross asymmetry in rates of fluid transfer with isotonic fluids depending on whether the luminal pressure was positive or negative; b) the observed magnitude of the negative luminal pressure required for the onset of secretion agreed with predictions; and c) the secretion contained significant amounts of protein at about 25% of the plasma concentration.     

NG-nitro-L-arginine methyl ester reduces senna- and cascara-induced diarrhoea and fluid secretion in the rat

Senna (60 mg/kg orally) and cascara (800 mg/kg orally)-induced diarrhoea and net fluid secretion were studied in rats for a time period of 1-8 h. NG-Nitro-L-arginine methyl ester (L-NAME) (2.5-25 mg/kg i.p. twice, 15 min before and 4 h after laxative administration), an inhibitor of nitric oxide synthase, reduced the diarrhoeal response. This effect was counteracted by L-arginine (600 and 1500 mg/kg i.p. 15 min before laxative administration), the precursor of nitric oxide (NO). The senna- and cascara-stimulated fluid secretion was reduced by NG-nitro-L-arginine methyl ester 25 mg/kg i.p. (twice, 15 min before and 4 h after laxative administration), while the stereoisomer NG-nitro-D-arginine methyl ester (D-NAME) 25 mg/kg i.p. was without effect. These results suggest a possible involvement of NO in senna- and cascara-induced diarrhoea and fluid secretion.     

Aldosterone secretion during high sodium cerebrospinal fluid perfusion of the brain ventricles

Conscious sheep with permanent indwelling cannulae in the lateral ventricles and the cisterna magna were Na depleted and then perfused for 9 h with an artificial CSF solution. There were 3 experimental groups: Group I (n=5) received perfusion with aritifical CSF containing NA 170 MEq./1, Group II (n=7) received perfusion with artificial CSF containing Na 145 mEq./1, Group III (n=7) received no perfusion. In Group I the blood aldosterone level fell from 26.4 +/- 7.4 to 8.6 +/- 2.3 ng/100 ml by 9 h after perfusion. There was no significant change in plasma [Na] or [K], blood angiotensin II or plasma renin concentration. Blood cortisol and corticosterone levels rose. There was also a fall in post-perfusion. Group III showed no significant change in blood aldosterone concentration. Multivariate statistical analysis showed that the fall in aldosterone levels during 170 mEq./l Na perfusion could not be accounted for by changes, either alone or together, of ACTH as evidenced by alteration in blood cortisol or corticosterone, or by change of plasma [Na], [K] or renin concentrations. This data supports the hypothesis of an additional factor which may be of CNS origin being involved in the control of aldosterone secretion.     

Role of cyclooxygenase-2 for fluid secretion by the inflamed gallbladder mucosa

Heterotrimeric GTP-binding protein (G-protein)-coupled receptors are able to induce a variety of responses including cell proliferation, differentiation, and activation of several intracellular kinase cascades. Prominent among these kinases are the activation of mitogen-activated protein (MAP) kinase, including the extracellular signal-regulated kinases (ERKs), ERK1 and ERK2 (p44mapk and p42mapk, respectively); stress-activated protein kinases (SAPKs/JNKs); and p38 kinase. These receptors signal through G-proteins. Recent data have shown that the activation of mitogen-activated protein/ERK kinase induced by G-protein-coupled receptors is mediated by both Galpha and Gbetagamma subunits involving a common signaling pathway with receptor-tyrosine-kinases. Gbetagamma-mediated mitogen-activated protein kinase activation is mediated by activation of phosphoinositide 3-kinase, followed by a tyrosine phosphorylation event, and proceeds in a sequence of events that involve functional association among the adaptor proteins Shc, Grb2, and Sos. SAPKs/JNKs and p38 are able to be activated by Gbetagamma proteins in a pathway involving Rho family proteins including RhoA, Rac1, and Cdc42.     

Effect of furosemide and intravenous normal saline fluid load upon the renal resistive index in nonobstructed kidneys in children

Recent literature has shown that relative to baseline the renal resistive index remains unchanged in nonobstructed kidneys and increases in obstructed kidneys after administration of furosemide. To our knowledge the effect upon the renal resistive index of furosemide administered in conjunction with intravenous normal saline fluid load has not been reported. We evaluated the renal resistive index in 13 nonobstructed kidneys in 8 children 6 to 18 years old before and after furosemide and intravenous normal saline fluid load. The mean resistive index decreased from baseline (mean decrease was 0.06 +/- 0.06 standard deviation), with the observation of a resistive index decrease significant to p < 0.005). It appears likely that the combination of an intravenous normal saline fluid load and furosemide caused the resistive index decrease, since a decrease was not observed with furosemide alone; however, these results cannot exclude the possibility that the resistive index decrease was due to the intravenous normal saline fluid load alone. Nonetheless, these data are important since they may provide the foundation for the development of a pharmacologically challenged Doppler sonographic examination using furosemide and intravenous normal saline fluid load to evaluate better potentially obstructed kidneys.     

Mechanism underlying histamine-induced desensitization of amylase secretion in rat parotid glands

1. Histamine acted on H2 receptors in rat parotid tissues and induced the amylase secretion. Immunoblot analysis by using anti-H2 receptor protein antiserum demonstrated that histamine induced the increase and decrease in the amounts of H2 receptor proteins in basolateral and intracellular membranes, respectively. 2. Short-term treatment with histamine resulted in decreases in amylase secretion, the density of H2 receptors and their affinity for the agonists during further incubation with histamine, but showed an unaltered secretory response to isoproterenol, indicating that the histamine-induced desensitization was confined to H2 receptors. 3. This treatment triggered a 20% decrease in the histamine-stimulated adenylate cyclase activity and a 40% decrease in the phosphorylation level of Gi2alpha protein in the tissues, resulting in an increase in pertussis toxin (IAP)-catalyzed ADP-ribosylation of the protein. An enhancement of cholera toxin-catalyzed ADP-ribosylation of Gs protein was observed only during the first incubation with histamine. 4. This treatment triggered a 30% decrease and a 60% increase in the histamine-stimulated activities of protein kinase A and protein phosphatase 2A in the tissues, respectively. 5. Pretreatment with okadaic acid completely blocked the histamine-induced decrease in amylase secretion and increase in IAP-catalyzed ADP-ribosylation of Gi protein. The levels of Gi2alpha and Gs alpha proteins in the tissues were not modified by histamine treatment and the level of Gi2alpha protein was not affected by pretreatment with okadaic acid, as assessed by immunoblot analyses with anti-Gi2alpha and anti-Gs alpha protein antiserum. 6. The regulation of Gi2alpha protein phosphorylation in parotid tissues plays an important role in the histamine-induced desensitization of amylase secretion.     

Radiation-induced progressive decrease in fluid secretion in rat submandibular glands is related to decreased acinar volume and not impaired calcium signaling

The mechanism(s) of radiation-induced salivary gland dysfunction is poorly understood. In the present study, we have assessed the secretory function (muscarinic agonist-stimulated saliva flow, intracellular calcium mobilization, Na+/K+/2Cl- cotransport activity) in rat submandibular glands 12 months postirradiation (single dose, 10 Gy). The morphological status of glands from control and irradiated rats was also determined. Pilocarpine-stimulated salivary flow was decreased by 67% at 12 months (but not at 3 months) after irradiation. This was associated with a 47% decrease in the wet weight of the irradiated glands. Histological and morphometric analysis demonstrated that acinar cells were smaller and occupied relatively less volume and convoluted granular tubules were smaller but occupied the same relative volume, while intercalated and striated ducts maintained their size but occupied a greater relative volume in submandibular glands from irradiated compared to control animals. In addition, no inflammation or fibrosis was observed in the irradiated tissues. Carbachol- or thapsigargin-stimulated mobilization of Ca2+ was similar in dispersed submandibular gland cells from control and irradiated animals. Further, [Ca2+]i imaging of individual ducts and acini from control and irradiated groups showed, for the first time, that mobilization of Ca2+ in either cell type was not altered by the radiation treatment. The carbachol-stimulated, bumetanide-sensitive component of the Na+/K+/ 2Cl- cotransport activity was also similar in submandibular gland cells from control and irradiated animals. These data demonstrate that a single dose of gamma radiation induces a progressive loss of submandibular gland tissue and function. This loss of salivary flow is not due to chronic inflammation or fibrosis of the gland or an alteration in the neurotransmitter signaling mechanism in the acinar or ductal cells. The radiation-induced decrease in fluid secretion appears to be related to a change in either the water-handling capacity of the acini or the number of acinar cells in the gland.     

alpha-Flupenthixol: an antagonist of dopamine-evoked fluid secretion by an insect salivary gland preparation

1 We have demonstrated inhibition of secretory responses of cockroach salivary glands to dopamine, adrenaline, noradrenaline and neurotransmitter by alpha-flupenthixol. This inhibition was slow in onset (60 min) and in reversal (greater than 2 h). 2 Inhibition of responses to adrenaline and noradrenaline was non-competitive, since the maxima and slopes of dose-response curves of these agonists were reduced. 3 Although at low concentrations (less than 3 microM) the antagonism of responses to dopamine showed some characteristics of competitive inhibition, at higher doses non-competitive inhibition was clearly demonstrated. 4 These results are explained in terms of different efficacies of the agonists for the receptors antagonized by alpha-flupenthixol. 5 beta-Flupenthixol was shown to antagonize responses to dopamine; however it was 10 to 100 times less potent than alpha-flupenthixol.     

Dissociated effect of sodium intake on glomerular and pressor responses to angiotensin

The influence of chronic and acute changes in sodium intake on pressor and glomerular capillary responses to angiotensin was studied. Scanning electron microscopy was used to observe the capillary changes in the superficial glomeruli. The results showed that both responses was sodium-dependent but in opposite directions. Low sodium intake diminished the pressor effect but enhanced the glomerular capillary response to administered angiotensin. On the contrary, a high sodium diet or a short perfusion of 0.9% NaC1 considerably diminished the sensitivity of the glomerular capillaries to angiotensin, whereas the systemic hypertensive effect was enhanced. Our results demonstrate that the systemic circulation and the capillaries of the superficial glomeruli react independently to angiotensin. This suggests that the superficial glomerular receptors differ from the systemic ones.