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NASA NTRS2008

Stereomicroscope Inspection of Polished Aluminum Collector 50684.0

The Genesis polished aluminum "kidney" collector was damaged during the hard landing of the capsule on September 8, 2004 in the Utah desert. The kidney was introduced into the Genesis (ISO class 4) cleanroom laboratory on November 4, 2004 and stored under nitrogen cover gas. The collector is currently fastened to a highly polished stainless steel plate for secure handling. Curatorial work at JSC has made successful subdivision and subsequent allocation of samples from the kidney.

Rodriquez, M. C.↗

NASA NTRS2001

Osmoregulation in marine mammals

Osmoregulation in marine mammals has been investigated for over a century; however, a review of recent advances in our understanding of water and electrolyte balance and of renal function in marine mammals is warranted. The following topics are discussed: (i) kidney structure and urine concentrating ability, (ii) sources of water, (iii) the effects of feeding, fasting and diving, (iv) the renal responses to infusions of varying salinity and (v) hormonal regulation. The kidneys of pinnipeds and cetaceans are reniculate in structure, unlike those of terrestrial mammals (except bears), but this difference does not confer any greater concentrating ability. Pinnipeds, cetaceans, manatees and sea otters can concentrate their urine above the concentration of sea water, but only pinnipeds and otters have been shown to produce urine concentrations of Na+ and Cl- that are similar to those in sea water. This could afford them the capacity to drink sea water and not lose fresh water. However, with few exceptions, drinking is not a common behavior in pinnipeds and cetaceans. Water balance is maintained in these animals via metabolic and dietary water, while incidental ingestion and dietary salt may help maintain electrolyte homeostasis. Unlike most other aquatic mammals, sea otters commonly drink sea water and manatees frequently drink fresh water. Among the various taxonomic groups of marine mammals, the sensitivity of the renin-angiotensin-aldosterone system appears to be influenced by the availability of Na+. The antidiuretic role of vasopressin remains inconclusive in marine mammals, while the natriuretic function of atrial natriuretic peptide has yet to be examined. Ideas on the direction of future studies are presented.

Non-NASA Center↗

NASA NTRS1972

Separate physiological roles for two isozymes of pyridine nucleotide-linked glycerol-3-phosphate dehydrogenase in chicken.

The isozymes considered are designated 'liver type' and 'muscle type' based on the tissue of highest concentration. Electrophoretic analysis shows that the liver type is found in small amounts or is undetectable in all tissues studied except liver. The muscle type is found in skeletal muscles and kidney. Presumptive hybrid enzymes occur at low levels in chicken liver and kidney. The tissue distribution of glyceron-3-P dehydrogenase in several birds capable of sustained flight is different than in chicken.

White, H. B., III↗

NASA NTRS1973

Role of atrial receptors in the control of sodium excretion

Responses of an innervated and a contralateral chronically denervated kidney to mild positive pressure breathing are compared for saline volume expansions in chloralose anesthetized dogs. It is shown that mild pressure breathing significantly reduces sodium excretion, urine flow, free water clearance, and PAH clearance. After 20 minutes of positive pressure breathing, both kidney responses are identical suggesting the release of natriuretic hormone which reduces renal function in addition to the demonstrated change in renal nerve activity. Increase of the left atrial pressure through balloon obstruction of the mitral orifice increases urine flow, sodium excretion and PAH clearance; inflation of the balloon and positive pressure breathing again depresses renal function. Preliminary evidence indicates that receptors in the right atrium are more severely affected by pressure breathing than those in the left atrium.

Meehan, J. R.↗

NASA NTRS1975

Evaluation of viscera and other tissues

Histopathological findings in the lungs, livers, bone marrows, small intestines, gonads, kidneys, and other tissues of the four pocket mice (Perognathus longimembris) that survived the Apollo XVII flight were evaluated in the light of their immediate environment and as targets of HZE cosmic ray particles. Results of this study failed to disclose changes that could be ascribed to the HZE particle radiation. Decreased numbers of erythropoietic cells in the bone marrow of the flight mice were probably related to the increased oxygen pressure. The small intestine showed no changes. Ovaries and testes appeared normal. Two of the three surviving male flight mice displayed early stages of spermatogenesis, just as ground-based controls did at the same season. Abnormalities were also not found in the thyroid, parathyroids, adrenals, or kidneys. The status of the juxtaglomerular apparatus could not be evaluated. The lungs exhibited nonspecific slight reactions. A variety of incidental lesions were noted in the livers of both the flight mice and their controls. The heart muscle showed nothing that could be regarded as pathological. Sections of skeletal muscle examined were free from significant change.

Ellis, J. T.↗

NASA NTRS1977

Separation of lymphocytes by electrophoresis under terrestrial conditions and at zero gravity, phase 3

Electrophoretic mobilities (EPM) of peripheral lymphocytes were studied from normal subjects, chronic hemodialysis patients and kidney transplant recipients. A technique to separate B lymphocytes and null cells from non-T lymphocyte preparation was developed. The experiments were designed to determine which subpopulation of the non-T lymphocytes is primarily affected and shows a decreased EPM in chronic hemodialysis patients and kidney transplant recipients.

Rubin, A. L.↗

NASA NTRS1978

Two-week studies of survivors from exposures to pyrolysis gases

Swiss Webster male mice which had survived near-lethal concentrations of pyrolysis gases from a variety of polymeric materials were killed two weeks after exposure, and the lungs, heart, liver, kidney, and spleen were examined. Microscopic examination revealed no significant effects on the liver, kidney, and spleen, while the effect on lungs could not be determined because of the high level of pathology in both experimental and control animals. The polymeric materials which were pyrolyzed were polyethylene, ABS, polycarbonate, polyaryl sulfone, polyether sulfone, polyphenylene sulfide, modified polyphenylene oxide, chlorinated polyvinyl chloride, polyvinylidene fluoride, and fluorene polycarbonate. It is suggested that tissue specimens should be examined 24 or 48 hr after exposure rather than 2 wks after exposure, since the 2 wk period permits healing to occur.

Bucci, T. J.↗

NASA NTRS1982

Electrophoresis tests on STS-3 and ground control experiments - A basis for future biological sample selections

Static zone electrophoresis is an electrokinetic method of separating macromolecules and small particles. However, its application for the isolation of biological cells and concentrated protein solutions is limited by sedimentation and convection. Microgravity eliminates or reduces sedimentation, floatation, and density-driven convection arising from either Joule heating or concentration differences. The advantages of such an environment were first demonstrated in space during the Apollo 14 and 16 missions. In 1975 the Electrophoresis Technology Experiment (MA-011) was conducted during the Apollo-Soyuz Test Project flight. In 1979 a project was initiated to repeat the separations of human kidney cells. One of the major objectives of the Electrophoresis Equipment Verification Tests (EEVT) on STS-3 was to repeat and thereby validate the first successful electrophoretic separation of human kidney cells. Attention is given to the EEVT apparatus, the preflight electrophoresis, and inflight operational results.

Morrison, D. R.↗

NASA NTRS1985

Cutting head for ultrasonic lithotripsy

A cutting head for attachment to the end of the wire probe of an ultrasonic kidney stone disintegration instrument is described. The cutting head has a plurality of circumferentially arranged teeth formed at one end thereof to provide a cup shaped receptacle for kidney stones encountered during the disintegration procedure. An integral reduced diameter collar diminishes stress points in the wire and reduce breakage thereof.

Anguluo, E. D.↗

NASA NTRS1987

Cutting Head for Ultrasonic Lithotripsy

Kidney stones lodged in urinary tract disintegrated with increased safety and efficiency by cutting head attached to end of vibrated wire probe. Aligns probe with stone and enables probe to vibrate long enough to disintegrate stone. Design of cutting head reduces risk of metal-fatigue-induced breakage of probe tip leaving metal fragments in urinary tract. Teeth of cutting head both seat and fragment kidney stone, while extension of collar into catheter lessens mechanical strain in probe wire, increasing probe life and lessening danger of in situ probe breakage.

Angulo, E. D.↗

NASA NTRS1988

Regulation of calcium metabolism during prolonged antiorthostatic hypokinesia

Characteristics of the regulation of calcium exchange in healthy persons exposed to 182 days of antiorthostatic hypokinesia are investigated. Total calcium concentrations, ionized calcium activities and parathyroid hormone concentrations in blood serum were determined, before, during, and up to 15 days after a 182-day period of strict bed rest at a head down tilt of 4 deg; and tests of blood urine responses to a calcium lactate stress were performed to study the role of the kidneys. An increase in calcium ion activity is observed during the period of hypokinesia, while total calcium concentrations changed to a lesser degree. Plasma parathyroid hormone levels are found to significantly exceed background levels during hypokinesia and in the recovery period immediately following. Finally, the increase in calcium excretion in the urine during prolonged limitations of muscular activity is found to be connected with both an enhancement of calcium filtration and a decrease in its reabsorption in the kidneys, possibly due to changes in hormonal regulation.

Grigoryev, A. I.↗

NASA NTRS1987

Renal effects of anti-gravity suit inflation in man in relation to cardiovascular and hormonal changes

It is shown that inflation for 3 hr of an antigravity suit that covered the legs and abdomen of normal standing subjects results in significant increases in urine flow, osmolar and free water clearances, total and fractional sodium excretion, and potassium excretion, while glomerular filtration rate and renal plasma flow are transiently increased. Such changes in kidney function are the consequence of the increase in thoracic blood volume induced by inflation which also results in an immediate increase in blood pressure and reflex bradycardia, together with a progressive lowering of plasma renin activity and aldosterone. The changes in kidney excretory patterns brought about by suit inflation appear to be similar in nature and magnitude to those observed during water immersion or in the early phase of bed rest, situations known to result in a headward redistribution of blood.

Geelen, G.↗

NASA NTRS1994

Role of Nitric Oxide in the Regulation of Renin and Vasopressin Secretion

Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, immune, and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, and anterior pituitary gland, and evidence is accumulating that it contributes to the regulation of the secretion of renin and vasopressin, hormones that play key roles in the control of sodium and water balance. Several lines of evidence have implicated nitric oxide in the control of renin secretion. The enzyme nitric oxide synthase is present in vascular and tubular elements of the kidney, particularly in cells of the macula densa, a structure that plays an important role in the control of renin secretion. Guanylyl cyclase, a major target for nitric oxide, is also present in the kidney. Drugs that inhibit nitric oxide synthesis generally suppress renin release in vivo and in vitro, suggesting a stimulatory role for the L-arginine/nitric oxide pathway in the control of renin secretion. Under some conditions, however, blockade of nitric oxide synthesis increases renin secretion. Recent studies indicate that nitric oxide not only contributes to the regulation of basal renin secretion, but also participates in the renin secretory responses to activation of the renal baroreceptor, macula densa, and beta adrenoceptor mechanisms that regulate renin secretion. Histochemical and immunocytochemical studies have revealed the presence of nitric oxide synthase in the supraoptic and paraventricular nuclei of the hypothalamus and in the posterior pituitary gland. Colocalization of nitric oxide synthase and vasopressin has been demonstrated in some hypothalamic neurons. Nitric oxide synthase activity in the hypothalamus and pituitary is increased by maneuvers known to stimulate vasopressin secretion, including salt loading and dehydration, Administration of L-arginine and nitric oxide donors in vitro and in vivo has variable effects on vasopressin secretion, but the most common one is inhibition. Blockade of nitric oxide synthesis has been reported to increase vasopressin secretion, but again variable results have been obtained. An attractive working hypothesis is that nitric oxide serves a neuromodulatory role as an inhibitor of vasopressin secretion.

Reid, Ian A.↗

NASA NTRS1983

On the Mechanism of Serotonin-Induced Dipsogenesis in the Rat

Subcutaneous administration of 1-5-hydroxytryptophan (5-HTP), the precursor of serotonin, to female rats induces copious drinking accompanied by activation of the renin-angiotensin system. Neither a reduction in blood pressure nor body temperature accompanied administration of 5-HTP. The objective of the present study was to determine whether serotonin-induced dipsogenesis, like that of 5-HTP, is mediated via the renin-angiotensin system. Serotonin (2 mg/kg, SC)-induced drinking was inhibited by the dopaminergic antagonist, haloperidol (150 /micro g/kg, IP), which also inhibits angiotensin II-induced drinking, Both captopril (35 mg/kg, IP), an angiotensin converting enzyme inhibitor, and propranolol (6 micro g/kg, IP), a beta-adrenergic antagonist, blocked serotonin-induced dipsogenesis. The alpha(sub a),-adrenergic agonist, clonidine (6.25 micro g/kg, SC), which suppresses renin release from the kidney, attenuated serotonin-induced water intake. The dipsogenic responses to submaximal concentrations of both serotonin (1 mg/kg, SC) and isoproterenol (8 micro g/kg, SC) were additive rather than interactive suggesting that similar pathways mediate both responses. The serotonergic receptor antagonist, methysergide (3 mg/kg, IP), inhibited serotonin-induced drinking but had no effect on isoproterenol (25micro g/kg, SC)-induced dipsogenesis. However, neither serotonin (2 mg/kg, SC) nor isoproterenol (25 micro g/kg, SC)-induced drinking was inhibited by cinansefin (25 micro g/kg, IP). These data indicate that serotonin induces drinking in rats via the renin-angiotensin system. However, the results of the studies using methysergide suggest that scrotonin appears to act at a point prior to activation of beta-adrenoceptors in the pathway leading to release of renin from the kidneys.

Kikta, Dianne C.↗

NASA NTRS1985

The Radioimmunoassay of Fluid and Electrolyte Hormones

The subject of the paper will be the assay of fluid/electrolyte hormones. ADH (antidiuretic hormone also referred to as vasopressin) reduces fluid loss by increasing water reabsorption by the kidney. The stimuli for its release from the pituitary are loss of blood, dehydration, or increased salt intake. Angiotensin II is the next hormone of interest. It is "generated" from a blood protein by the release of renin from the kidney. One of its functions is to stimulate the secretion of aldosterone from the adrenal gland. Release of renin is also stimulated by volume and sodium loss.

Keil, Lanny C.↗

NASA NTRS2002

Plasma 24,25-dihydroxyvitamin D concentration of Dahl salt-sensitive rats decreases during high salt intake

Dahl salt-sensitive rats, but not salt-resistant rats, develop hypertension in response to high salt intake. We have previously shown an inverse relationship between plasma 25-hydroxyvitamin D (25-OHD) concentration and blood pressure of Dahl salt-sensitive rats during high salt intake. In this study, we report on the relationship between high salt intake and plasma 24,25-dihydroxyvitamin D (24,25-(OH)(2)D) concentration of Dahl salt-sensitive and salt-resistant rats. Rats were fed a high salt diet (8%) and sacrificed at day 2, 7, 14, 21, and 28. Plasma 24,25-(OH)(2)D concentrations of salt-sensitive rats were reduced to 50% of that at baseline at day 2-when blood pressure and plasma 25-OHD concentration were unchanged, but 25-OHD content in the kidney was 81% of that at baseline. Plasma 24,25-(OH)(2)D concentration was reduced further to 10% of that at baseline from day 7 to 14 of high salt intake, a reduction that was prevented in rats switched to a low salt (0.3%) diet at day 7. Exogenous 24,25-dihydroxycholecalciferol (24,25-(OH)(2)D(3)), administered at a level that increased plasma 24,25-(OH)(2)D concentration to five times normal, did not attenuate the salt-induced hypertension of salt-sensitive rats. Plasma 24,25-(OH)(2)D concentration of salt-resistant rats was gradually reduced to 50% of that at baseline at day 14 and returned to baseline value at day 28 of high salt intake. We conclude that the decrease in plasma 24,25-(OH)(2)D concentration in salt-sensitive rats during high salt intake is caused by decreased 25-OHD content in the kidney and also by another unidentified mechanism.

Non-NASA Center↗

NASA NTRS2002

Parathyroid hormone-dependent signaling pathways regulating genes in bone cells

Parathyroid hormone (PTH) is an 84-amino-acid polypeptide hormone functioning as a major mediator of bone remodeling and as an essential regulator of calcium homeostasis. PTH and PTH-related protein (PTHrP) indirectly activate osteoclasts resulting in increased bone resorption. During this process, PTH changes the phenotype of the osteoblast from a cell involved in bone formation to one directing bone resorption. In addition to these catabolic effects, PTH has been demonstrated to be an anabolic factor in skeletal tissue and in vitro. As a result, PTH has potential medical application to the treatment of osteoporosis, since intermittent administration of PTH stimulates bone formation. Activation of osteoblasts by PTH results in expression of genes important for the degradation of the extracellular matrix, production of growth factors, and stimulation and recruitment of osteoclasts. The ability of PTH to drive changes in gene expression is dependent upon activation of transcription factors such as the activator protein-1 family, RUNX2, and cAMP response element binding protein (CREB). Much of the regulation of these processes by PTH is protein kinase A (PKA)-dependent. However, while PKA is linked to many of the changes in gene expression directed by PTH, PKA activation has been shown to inhibit mitogen-activated protein kinase (MAPK) and proliferation of osteoblasts. It is now known that stimulation of MAPK and proliferation by PTH at low concentrations is protein kinase C (PKC)-dependent in both osteoblastic and kidney cells. Furthermore, PTH has been demonstrated to regulate components of the cell cycle. However, whether this regulation requires PKC and/or extracellular signal-regulated kinases or whether PTH is able to stimulate other components of the cell cycle is unknown. It is possible that stimulation of this signaling pathway by PTH mediates a unique pattern of gene expression resulting in proliferation in osteoblastic and kidney cells; however, specific examples of this are still unknown. This review will focus on what is known about PTH-mediated cell signaling, and discuss the established or putative PTH-regulated pattern of gene expression in osteoblastic cells following treatment with catabolic (high) or anabolic (low) concentrations of the hormone.

NASA Discipline Musculoskeletal↗

NASA NTRS1998

Mouse osteoblastic cell line (MC3T3-E1) expresses extracellular calcium (Ca2+o)-sensing receptor and its agonists stimulate chemotaxis and proliferation of MC3T3-E1 cells

The calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays key roles in extracellular calcium ion (Ca2+o) homeostasis in parathyroid gland and kidney. Osteoblasts appear at sites of osteoclastic bone resorption during bone remodeling in the "reversal" phase following osteoclastic resorption and preceding bone formation. Bone resorption produces substantial local increases in Ca2+o that could provide a signal for osteoblasts in the vicinity, leading us to determine whether such osteoblasts express the CaR. In this study, we used the mouse osteoblastic, clonal cell line MC3T3-E1. Both immunocytochemistry and Western blot analysis, using an antiserum specific for the CaR, detected CaR protein in MC3T3-E1 cells. We also identified CaR transcripts in MC3T3-E1 cells by Northern analysis using a CaR-specific riboprobe and by reverse transcription-polymerase chain reaction with CaR-specific primers, followed by nucleotide sequencing of the amplified products. Exposure of MC3T3-E1 cells to high Ca2+o (up to 4.8 mM) or the polycationic CaR agonists, neomycin and gadolinium (Gd3+), stimulated both chemotaxis and DNA synthesis in MC3T3-E1 cells. Therefore, taken together, our data strongly suggest that the osteoblastic cell line MC3T3-E1 possesses both CaR protein and mRNA very similar, if not identical, to those in parathyroid and kidney. Furthermore, the CaR in these osteoblasts could play a key role in regulating bone turnover by stimulating the proliferation and migration of such cells to sites of bone resorption as a result of local release of Ca2+o.

Non-NASA Center↗