Quantitative analysis of renal medullary anatomy in rats and rabbits

Knepper, Mark A.; Danielson, Robert; Saidel, Gerald M.; Post, Robert S.

doi:10.1038/ki.1977.118

Cited by 203 publications

(138 citation statements)

References 18 publications

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“…The model also predicts that only half of the arteriole/venule arcade pairs have an accompanying IL and that each muscle fiber within the fascicle is associated with two capillaries. The fact that five fascicles feed each lymphatic is strikingly similar to the arrangement of tubules feeding the cortical collecting duct (CCD), where five closely spaced tubules feed each CCD at the corticomedullary junction in both the rat and rabbit (13). The IL and the CCD play similar roles in that both are low-pressure drainage structures for a much larger organ.…”

Section: Discussionmentioning

confidence: 76%

Quantitative model for predicting lymph formation and muscle compressibility in skeletal muscle during contraction and stretch

Causey

Cowin

Weinbaum

2012

Proc. Natl. Acad. Sci. U.S.A.

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Skeletal muscle is widely perceived as nearly incompressible despite the fact that blood and lymphatic vessels within the endomysial and perimysial spaces undergo significant changes in diameter and length during stretch and contraction. These fluid shifts between fascicle and interstitial compartments have proved extremely difficult to measure. In this paper, we propose a theoretical framework based on a space-filling hexagonal fascicle array to provide predictions of the displacement of blood and lymph into and out of the muscle's endomysium and perimysium during stretch and contraction. We also use this model to quantify the distribution of blood and initial lymphatic (IL) vessels within a fascicle and its perimysial space using data for the rat spinotrapezius muscle. On average, there are 11 muscle fibers, 0.4 arteriole/venule pairs, and 0.2 IL vessels per fascicle. The model predicts that the blood volume in the endomysial space increases 24% and decreases 22% for a 20% contraction and stretch, respectively. However, these significant changes in blood volume in the endomysium produce a change of only ∼2% in fascicle cross-sectional area. In contrast, the entire muscle deviates from isovolumetry by 7% and 6% for a 20% contraction and stretch, respectively, largely attributable to the significantly larger blood volume changes that occur in the perimysial space. This suggests that arcade blood vessels in the perimysial space provide the primary pumping action required for the filling and emptying of ILs during muscular contraction and stretch.dimensions | spacing | resting | isovolumetric | deformation I n the 17th century, Jan Swammerdam placed an isolated frog's thigh muscle in an airtight syringe and measured the volume of the muscle as it contracted and relaxed by observing the movement of a droplet of water in the end of the syringe, thus inventing the first plethysmograph. He observed that the volume of the muscle did not change as it was excited. Thus, when a muscle is isolated so that blood neither enters nor exits the muscle, it functions isovolumetrically (1). Furthermore, because the bulk modulus of water is 2.3 GPa, its resistance to volumetric deformation is very large relative to its resistance to shape distortion, and muscle tissue itself is often described accurately as "incompressible." However, the entire muscle and parts of the muscle may experience volumetric changes attributable to the fact that both blood and lymph reside in highly flexible vessels in which they can both enter and exit with little resistance. These fluid conduits lie in both the endomysial space between individual muscle fibers within fascicles and in the perimysial space surrounding and separating the fascicles (Fig. 1A). The endomysial space contains capillaries, terminal arterioles (TAs), and collecting venules (CVs). Initial lymphatic (IL) vessels are occasionally seen in the capillary bed adjacent to muscle fibers; however, it is unclear if these vessels are involved in lymph formation and transport (2). The perimysi...

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Section: Discussionmentioning

confidence: 76%

Quantitative model for predicting lymph formation and muscle compressibility in skeletal muscle during contraction and stretch

Causey

Cowin

Weinbaum

2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Results from our previous study (4) (20,35). According to our present observations, because a similar or even higher ratio holds for the outer medulla of the mouse kidney, it is likely that most of the adenylate cyclase activity measured in homogenates prepared from mouse medulla represents predominantly adenylate cyclase from the ascending limbs of Henle's loops, whereas only a small proportion is derived from the collecting tubules.…”

Section: Discussionmentioning

confidence: 78%

Cellular Action of Vasopressin in Medullary Tubules of Mice with Hereditary Nephrogenic Diabetes Insipidus

Jackson¹,

Edwards²,

Valtin³

et al. 1980

J. Clin. Invest.

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A B S T R A C T Our previous studies (1974. J. Clin. suggested that impaired metabolism ofcyclic AMP (cAMP) may be involved in the renal unresponsiveness to vasopressin (VP) in mice with hereditary nephrogenic diabetes insipidus (NDI). To localize such a defect to specific segments of the nephron, we studied the activities of VP-sensitive adenylate cyclase, cAMP phosphodiesterase (cAMP-PDIE), as well as accumulation of cAMP in medullary collecting tubules (MCT) The results of the present in vitro experiments suggest that the functional unresponsiveness of NDI mice to VP is perhaps mainly the result of the inability of collecting tubules to increase intracellular cAMP levels in response to VP. In turn, this inability to increase cAMP in response to VP is at least partly the result of abnormally high activity of cAMP-PDIE, a somewhat lower activity of VP-sensitive adenylate cyclase in MCT of NDI mice, and perhaps to a deficiency of some other as yet unidentified factors. The possible contribution of low VP-sensitive adenylate cyclase activity in MAL of NDI mice to the renal resistance to VP remains to be defined. INTRODUCTIONOne animal model that phenotypically closely resembles human hereditary nephrogenic diabetes insipidus (NDI)l is a strain of mouse (so-called DI +/+ severe) with an inherited, vasopressin (VP)-resistant urinary concentrating defect (1)(2)(3)(4). Because administration of VP to NDI mice fails to increase osmolality of hypotonic urine (2, 3), these functional features indicate that collecting tubules failed to increase water permeability in response to the hormone. It is well established that the hydroosmotic effect of VP in collecting tubules (5-8) is mediated by adenosine 3',5'-cyclic monophosphate (cAMP) (5-7), and we have previously investigated the possibility that unresponsiveness to VP in NDI mice might be the

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“…Volumetrically, the mTAL is the dominant structure in the renal outer medulla (4). mTAL suspensions showed further enrichment of the TAL marker protein NKCC2 with respect to the whole outer medulla, although residual amounts of the collecting duct water channel AQP2 and the descending limb water channel AQP1 were present (Fig.…”

Section: Resultsmentioning

confidence: 99%

Quantitative phosphoproteomic analysis reveals cAMP/vasopressin-dependent signaling pathways in native renal thick ascending limb cells

Gunaratne

Braucht

Rinschen

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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103

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Quantitative mass spectrometry was used to identify hormonedependent signaling pathways in renal medullary thick ascending limb (mTAL) cells via phosphoproteomic analysis. Active transport of NaCl across the mTAL epithelium is accelerated by hormones that increase cAMP levels (vasopressin, glucagon, parathyroid hormone, and calcitonin). mTAL suspensions from rat kidneys were exposed (15 min) to a mixture of these four hormones. Tryptic phosphopeptides (immobilized metal affinity chromatography-enriched) were identified and quantified by mass spectrometry (LTQ-Orbitrap) using label-free methodology. We quantified a total of 654 phosphopeptides, of which 414 were quantified in three experimental pairs (hormone vs. vehicle). Of these phosphopeptides, 82% were statistically unchanged in abundance in response to the hormone mixture. In contrast, 48 phosphopeptides were significantly increased, whereas 28 were significantly decreased. The population of up-regulated phosphopeptides was highly enriched in basophilic kinase substrate motifs (AGC or calmodulin-sensitive kinase families), whereas the down-regulated sites were dominated by "proline-directed" motifs (cyclin-dependent or MAP kinase families). Bioinformatic classification uncovered overrepresentation of transmembrane transporters, protein phosphatase regulators, and cytoskeletal binding proteins among the regulated proteins. Immunoblotting with phospho-specific antibodies confirmed cAMP/vasopressin-dependent phosphorylation at Thr96, Ser126, and Ser874 of the Na + :K + :2Cl − cotransporter NKCC2, at Ser552 of the Na + :H + exchanger NHE3, and at Ser552 of β-catenin. Vasopressin also increased phosphorylation of NKCC2 at both Ser126 (more than fivefold) and Ser874 (more than threefold) in rats in vivo. Both sites were phosphorylated by purified protein kinase A during in vitro assays. These results support the view that, although protein kinase A plays a central role in mTAL signaling, additional kinases, including those that target proline-directed motifs, may be involved.protein phosphatase | glucose transporters | mass spectrometry | ion transporters | protein kinase T he thick ascending limb (TAL) of Henle's loop is a nephron segment that plays a critical role in the control of mammalian water excretion. Active NaCl transport by the medullary TAL (mTAL) drives the countercurrent multiplication process that concentrates the urine (1). Hormones that increase the concentration of the intracellular second messenger, cAMP, have been shown to enhance the rate of NaCl transport in mTAL cells (2). These hormones include parathyroid hormone (PTH), calcitonin, glucagon, and vasopressin (2). Among these, only vasopressin plays a selective role in regulation of water balance. The molecular targets for cAMP-mediated regulation in the mTAL include the apical Na + : K + :2Cl − cotransporter NKCC2 (gene symbol: Slc12a1) and the apical Na + :H + exchanger NHE3 (Slc9a3) (3).The signaling network that accounts for cAMP-dependent regulation of these transporters is largely unk...

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Quantitative analysis of renal medullary anatomy in rats and rabbits

Cited by 203 publications

References 18 publications

Quantitative model for predicting lymph formation and muscle compressibility in skeletal muscle during contraction and stretch

Quantitative model for predicting lymph formation and muscle compressibility in skeletal muscle during contraction and stretch

Cellular Action of Vasopressin in Medullary Tubules of Mice with Hereditary Nephrogenic Diabetes Insipidus

Quantitative phosphoproteomic analysis reveals cAMP/vasopressin-dependent signaling pathways in native renal thick ascending limb cells

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