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Quantitative aspects of reversible osmotic opening of the blood-brain barrier.

Retrograde infusion of a hypertonic arabinose solution into the right external carotid artery of rats reversibly increases cerebrovascular permeability to [14C]sucrose in the right cerebral hemisphere. PA ([14C]sucrose permeability x capillary surface area) rises from a control mean of 11 x 10(-6) S-1 to above 200 x 10(-6) S-1. The rise correlates with an increased staining of the brain by intravascular Evans blue, and is followed by a transient, 1-1.5% increase in brain water content. At least 20 s of infusion is required for 1.6 M arabinose solution to effectively open the blood-brain barrier. The increase in cerebrovascular permeability is temporary, however, because PA remains slightly elevated 1-2 h after infusion and is normal 6 h after infusion. It is suggested that osmotic barrier opening is mediated by cerebrovascular dilatation as well as by shrinkage of the vascular endothelium. By quantitatively defining thresholds of infusate concentration and infusion time for osmotic barrier opening, and by characterizing the time course of increased PA, the experiments establish criteria for applying the osmotic method to experimental pharmacology of the central nervous system.

Animals↗

Osmotically sensitive renin release from permeabilized juxtaglomerular cells.

Renin secretion from juxtaglomerular (JG) cells is sensitive to external osmolality in a way that has been suggested to depend either on cellular volume or on effects on secretory granules. To distinguish between these possibilities, a technique for permeabilization of JG cell membranes was developed. Rat glomeruli with attached JG cells were isolated and permeabilized by 20 microM digitonin for 12 min and followed by continuous exposure to 2 microM digitonin. Experiments on proximal tubules showed that cellular volume was unaffected by changes in external sucrose concentration after a similar permeabilization procedure. With permeabilized JG cells the following changes in osmolality were tested (in mM sucrose): +90 (n = 6), +60 (n = 5), +30 (n = 6), +15 (n = 6), -15 (n = 5), -30 (n = 6), -60 (n = 6), and -90 (n = 6). With nonpermeabilized cells similar experiments were done with changes of +90 (n = 7), +30 (n = 4), -30 (n = 4), and -90 (n = 6) mM sucrose. Increases in osmolality caused inhibition of renin release, whereas decreases stimulated secretion. Within +/- 10% variations in osmolality there were no differences between the responses in permeabilized and intact cells, whereas the responses with larger changes were less in the permeabilized cells. Increase or decrease in urea concentration by 30 mM did not affect renin release. Thus water fluxes can influence renin release by a mechanism that is independent of cell volume.

Animals↗

Effect of papaverine on pulmonary vascular permeability to proteins.

Previous studies have suggested that papaverine, a drug commonly used in studies of transvascular fluid and solute exchange to eliminate confounding effects of changes in vascular tone, may itself increase vascular permeability. In this study, we determined the ability of papaverine to alter pulmonary vascular protein permeability by measuring the osmotic reflection coefficient (sigma) for total proteins in a canine isolated perfused left lower lung lobe (LLL) preparation. The reflection coefficient, determined by the hematocrit-protein double-indicator technique, for control LLL's was 0.83 +/- 0.04 (SE) (n = 7). In separate groups of LLL's, blood papaverine HCl concentrations of 10(-5), 10(-4), and 10(-3) M resulted in sigma's of 0.84 +/- 0.02 (n = 6), 0.73 +/- 0.04 (n = 7), and 0.53 +/- 0.04 (n = 6), respectively. When two LLL's from the 10(-4) M group with sigma's of 0.56 and 0.57 were excluded from the analysis, the average sigma for this group was 0.79 +/- 0.02. We conclude that papaverine increases protein permeability at a concentration of 10(-3) M but does so in only some lobes at 10(-4) M. These results suggest that caution be taken when using high concentrations of papaverine in fluid balance studies.

Animals↗

A membrane defect in cystic fibrosis: decreased red cell permeability to water.

The abnormally high concentrations of electrolytes and organic solutes found in the glandular secretions of individuals with cystic fibrosis may arise from decreased water content rather than perturbed solute transport. Thus, it is possible that the abnormalities insolute concentrations are a result of a reduced water movement into the secretory product. It is our hypothesis that if an abnormality exists in the transport of water across secretory cell membranes, this defect may also be expressed in nonsecretory cell membrane permeability to water. We report here osmotic water permeability measurements on red cells and 11 cystic fibrosis patients ranging in age from 2 to 20 years and eight normal individuals. The mean hydraulic conductivity for the patients of 1.23 +/- 0.13 cm3/dyne sec is significantly less (P < 0.001) than that of normal individuals who have permeabilities of 1.45 +/- 0.11 cm3/dyne sec. Analysis showed that the osmotic water permeability correlates well with the Shwachman score (r = 0.76). Patients who are in the poorest clinical condition show the lowest hydraulic conductivities.

Body Water↗

Effects of cadmium of the hydro-osmotic and natriferic responses to the toad bladder to vasopressin.

Cadmium, 10(-3) mol/l on the mucosal or 10(-5) mol/l on the serosal side of the toad urinary bladder, inhibits the hydro-osmotic effect of vasopressin. This inhibition is irreversible. The osmotic transfer of water in the absence of vasopressin was unaffected by the presence of the Cd2+. The hydro-osmotic response to cyclic AMP was also reduced by the Cd2+, but the response due to hypertonicity of the serosal bathing solution was unaffected. The short-circuit current (reflecting active transmural Na+ transport) was inhibited by 10(-3) mol Cd2+/l on the serosa, but was increased by 10(-3) mol/l at the mucosa or 10(-4) mol/l at the serosa. The natriferic response of the bladder to vasopressin was unaffected when Cd2+ was present under conditions that inhibited the hydro-osmotic response, further emphasizing that separate effector mechamisms may be involved for each effect.

Animals↗

[Ultrastructural changes in the cells of the vasopressin-sensitive epithelia during the stimulation of water transport].

The author's own and literary data are reviewed on the ultrastructural changes in cells of tight epithelia at the stimulation of osmotic water flows by vasopressin. The results of the relevant morphofunctional studies proved the idea of the transcellular water transport, being the following: 1) the absence of structural changes of tight junction under big water flows; 2) the appearance of domains with high water permeability (aggregates of IMP) in the apical membranes of cells transporting water; 3) changes in the vacuolar system of cells resulting in the appearance of gigantic vacuoles involved in transcellular water transport and in osmoregulation; 4) the redistribution of microfilaments and the enlargement of microtubules during the water transport. Hypotheses are discussed accounting for the origin of water channels from intracellular sources (aggrephores or/and granules); in addition, structural peculiarities and genesis of gigantic vacuoles are considered.

Animals↗

Cell physiological effects of radiofrequency electromagnetic fields.

Ovarian and body cavity eggs from R. temporaria were exposed to radiofrequency (rf) electromagnetic fields in the frequency range 10-27 MHz with specific absorption rates (SAR) up to 800 W/kg. The effect of the exposure was investigated by measurement of the water-related cell physiological parameters, isotopic and osmotic water membrane permeability and density of the egg cells. Only the osmotic water permeability, Pf, of ovarian eggs was significantly altered. A decrease of about 30% was seen for SARs of 50 W/kg and exposure times up to 2 h. Tests ruled out that the effect was due to temperature increase during the exposure. The observed decrease of Pf was most likely due to cloudy swelling of the egg cytoplasm resulting from the rf irradiation.

Animals↗