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  • 1
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Journal of the American Society of Nephrology Vol. 18, No. 1 ( 2007-01), p. 143-154
    In: Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 18, No. 1 ( 2007-01), p. 143-154
    Type of Medium: Online Resource
    ISSN: 1046-6673
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 2029124-3
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  • 2
    Online Resource
    Online Resource
    American Physiological Society ; 2000
    In:  American Journal of Physiology-Regulatory, Integrative and Comparative Physiology Vol. 278, No. 3 ( 2000-03-01), p. R556-R562
    In: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 278, No. 3 ( 2000-03-01), p. R556-R562
    Abstract: Experiments were performed to determine if there is regional heterogeneity in sympathetic neural activation of peripheral tissues in rats with chronic heart failure (HF; 6–8 wk after coronary artery ligation). Norepinephrine (NE) turnover, an index of sympathetic activation, was determined on the basis of the decline in tissue NE levels that occurs during the 8-h after tyrosine hydroxylase inhibition (α-methyl-dl-p-tyrosine, 300 mg/kg ip at 4-h intervals). Compared with sham-operated rats, NE turnover was increased in the cardiac left ventricle, skeletal muscle, duodenum, and kidney of rats with HF, but was unaltered in liver and spleen. The increased renal NE turnover in HF was largely a reflection of increased turnover in the cortex, with no change evident in the medulla. Blockade of sympathetic ganglionic traffic (hexamethonium, 2 mg/kg sc at 2-h intervals) eliminated the tissue-specific effects of HF on tissue NE levels measured 8-h after tyrosine hydroxylase inhibition. These data support the contention that chronic HF evokes a central nervous system-mediated increase in basal sympathetic tone that exhibits regional heterogeneity (both between and within organs), a phenomenon that likely contributes to the functional consequences of this pathophysiological state.
    Type of Medium: Online Resource
    ISSN: 0363-6119 , 1522-1490
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2000
    detail.hit.zdb_id: 1477297-8
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  • 3
    Online Resource
    Online Resource
    American Physiological Society ; 1988
    In:  American Journal of Physiology-Renal Physiology Vol. 254, No. 6 ( 1988-06-01), p. F926-F926
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 254, No. 6 ( 1988-06-01), p. F926-F926
    Abstract: Page F440: Peter J. Veldkamp, Pamela K. Carmines, Edward W. Inscho, and L. Gabriel Navar. “Direct evaluation of the microvascular actions of ANP in juxtamedullary nephrons.” Page F442: because of the disappointing quality of Fig. 1, the figure is reproduced here. (See PDF)
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    Language: English
    Publisher: American Physiological Society
    Publication Date: 1988
    detail.hit.zdb_id: 1477287-5
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  • 4
    Online Resource
    Online Resource
    American Physiological Society ; 2001
    In:  American Journal of Physiology-Renal Physiology Vol. 280, No. 4 ( 2001-04-01), p. F583-F591
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 280, No. 4 ( 2001-04-01), p. F583-F591
    Abstract: Experiments were performed to evaluate the hypothesis that opening of Ca 2+ -activated K + channels (BK Ca channels) promotes juxtamedullary arteriolar dilation and curtails constrictor responses to depolarizing agonists. Under baseline conditions, afferent and efferent arteriolar lumen diameters averaged 23.4 ± 0.9 ( n = 36) and 22.8 ± 1.1 ( n= 13) μm, respectively. The synthetic BK Ca channel opener NS-1619 evoked concentration-dependent afferent arteriolar dilation. BK Ca channel blockade (1 mM tetraethylammonium; TEA) decreased afferent diameter by 15 ± 3% and prevented the dilator response to 30 μM NS-1619. ANG II (10 nM) decreased afferent arteriolar diameter by 44 ± 4%, a response that was reduced by 30% during NS-1619 treatment; however, TEA failed to alter afferent constrictor responses to either ANG II or arginine vasopressin. Neither NS-1619 nor TEA altered agonist-induced constriction of the efferent arteriole. Thus, although the BK Ca channel agonist was able to curtail afferent (but not efferent) arteriolar constrictor responses to ANG II, BK Ca channel blockade did not allow exaggerated agonist-induced arteriolar constriction. These observations suggest that the BK Ca channels evident in afferent arteriolar smooth muscle do not provide a prominent physiological brake on agonist-induced constriction under our experimental conditions.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2001
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  • 5
    Online Resource
    Online Resource
    American Physiological Society ; 2001
    In:  American Journal of Physiology-Regulatory, Integrative and Comparative Physiology Vol. 281, No. 1 ( 2001-07-01), p. R239-R245
    In: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 281, No. 1 ( 2001-07-01), p. R239-R245
    Abstract: Experiments were performed to test the hypothesis that the renal interstitial hydrostatic pressure (RIHP) response to acute volume expansion is suppressed in diabetes mellitus. Sprague-Dawley rats received streptozotocin (STZ rats; 65 mg/kg ip) or vehicle (Sham rats). Two weeks later, RIHP and Na + excretion responses to acute graded volume expansion with isotonic saline were quantified under Inactin anesthesia (0.1 mg/kg ip). In Sham rats, acute graded volume expansion to 10% body wt produced increases in RIHP (Δ = 12.2 ± 2.4 mmHg), urine flow (Δ = 54 ± 8 μl · min −1 · g −1 ), and Na + excretion (Δ = 11.5 ± 1.9 μeq · min −1 · g −1 ). In STZ rats, these volume expansion-induced responses were significantly blunted (RIHP by 50%, urine flow by 81%, and Na + excretion by 76%). Renal decapsulation eliminated the differences between STZ and Sham rats with regard to volume expansion-induced increases in RIHP, urine flow, and Na + excretion. Renal denervation normalized the RIHP response to volume expansion and improved the diuretic and natriuretic responses in STZ rats. Moreover, diuretic and natriuretic responses to direct changes in RIHP (induced by renal interstitial volume expansion) were blunted in STZ rats. We conclude that diminished alterations in RIHP, as well as a reduced impact of RIHP on Na + excretion, contribute to the impaired diuretic and natriuretic responses to acute volume expansion during the early stage of diabetes.
    Type of Medium: Online Resource
    ISSN: 0363-6119 , 1522-1490
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2001
    detail.hit.zdb_id: 1477297-8
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  • 6
    Online Resource
    Online Resource
    American Physiological Society ; 2005
    In:  American Journal of Physiology-Renal Physiology Vol. 288, No. 1 ( 2005-01), p. F82-F90
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 288, No. 1 ( 2005-01), p. F82-F90
    Abstract: Shear stress increases nitric oxide (NO) production by endothelial cells, inner medullary collecting duct cells, and thick ascending limb. We postulated that the osmotic diuresis accompanying type 1 diabetes is associated with increased NO synthase (NOS) activity and/or expression in the renal medulla. Diabetes was induced by injection of streptozotocin, with insulin provided to maintain moderate hyperglycemia (Hyp) or euglycemia (Eug) for 3 wk. Sham rats received vehicle treatments. A separate group of rats (Phz) received phlorizin to produce a glucose-dependent osmotic diuresis. Renal medullary NOS1 and NOS2 activities did not differ between groups, whereas NOS3 activity was significantly increased in Hyp. Neither NOS1 nor NOS3 protein levels differed significantly between groups. Reduced phosphorylation of NOS3 at Thr 495 and Ser 633 was evident in medullary homogenates from Hyp rats, with no difference apparent at Ser 1177 . Immunohistochemical analysis indicated prominent expression of pThr 495 NOS3 in the thick ascending limb and collecting duct of Sham and Phz rats. Hyp rats displayed staining in the collecting duct but minimal thick ascending limb staining. Immunostaining with anti-pSer 1177 NOS3 was evident only in the thick ascending limb, with no apparent differences between groups. In summary, glucose-dependent osmotic diuresis alone did not alter NOS activity or expression in the renal medulla. Diabetic hyperglycemia increased medullary NOS3 activity without a concomitant increase in NOS3 protein levels; however, NOS3 phosphorylation was reduced at Thr 495 and Ser 633 . Thus changes in the phosphorylation of NOS at known regulatory sites might represent the primary mechanism underlying increased renal medullary NOS activity in diabetic hyperglycemia.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2005
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  • 7
    Online Resource
    Online Resource
    American Physiological Society ; 2000
    In:  American Journal of Physiology-Renal Physiology Vol. 278, No. 6 ( 2000-06-01), p. F954-F961
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 278, No. 6 ( 2000-06-01), p. F954-F961
    Abstract: Experiments were performed to identify the biophysical properties of store-operated Ca 2+ channels (SOC) in cultured human glomerular mesangial cells (MC). A fluorometric technique (fura 2) was utilized to monitor the change in intracellular calcium concentration ([Ca 2+ ] i ) evoked by elevating external [Ca 2+ ] from 10 nM to 1 mM (Δ[Ca 2+ ]). Under control conditions, Δ[Ca 2+ ] averaged 6 nM and was unaffected by elevating bath [K + ]. After treatment with 1 μM thapsigargin to deplete the intracellular Ca 2+ store, the change in [Ca 2+ ] i (Δ[Ca 2+ ] th ) averaged 147 ± 16 nM. In thapsigargin-treated MC studied under depolarizing conditions (75 mM bath K + ), Δ[Ca 2+ ] th was 45 ± 7 nM. The Δ[Ca 2+ ] th response of thapsigargin-treated cells was inhibited by La 3+ (IC 50 = 335 nM) but was unaffected by 5 μM Cd 2+ . In patch clamp studies, inward currents were observed in cell-attached patches with either 90 mM Ba 2+ or Ca 2+ in the pipette and 140 mM KCl in the bathing solution. The single-channel conductance was 2.1 pS with Ba 2+ and 0.7 pS with Ca 2+ . The estimated selectivities were Ca 2+ 〉 Ba 2+ 〉 〉 K + . These channels were sensitive to 2 μM La 3+ , insensitive to 5 μM Cd 2+ , and voltage independent, with an average channel activity ( NP o ) of 1.02 at command potential (− V p ) ranging from 0 to −80 mV. In summary, MC exhibited an electrogenic Ca 2+ influx pathway that is suggestive of Ca 2+ entry through SOC, as well as a small-conductance divalent-selective channel displaying biophysical properties consistent with SOC. Based on estimates of whole cell Ca 2+ influx derived from our data, we conclude that SOC with low single-channel conductance must be highly abundant in MC to allow significant capacitative Ca 2+ entry in response to depletion of the intracellular store.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2000
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  • 8
    Online Resource
    Online Resource
    American Physiological Society ; 2009
    In:  American Journal of Physiology-Renal Physiology Vol. 297, No. 2 ( 2009-08), p. F471-F480
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 297, No. 2 ( 2009-08), p. F471-F480
    Abstract: Calcineurin (PP2B) has recently been shown to be upregulated in the medullary thick ascending limb (mTAL) during diabetes. The mTAL expresses all three isoforms of nitric oxide synthase (NOS), which are subject to phosphoregulation and represent substrates for PP2B. Therefore, we hypothesized that diabetes induces PP2B-dependent upregulation of NOS activity and NO production in the mTAL. Three weeks after injection of streptozotocin (STZ rats) or vehicle (sham rats), mTAL suspensions were prepared for use in functional and biochemical assays. PP2B activity and expression were increased in mTALs from STZ rats compared with sham. Nitrite production was significantly reduced in mTALs from STZ rats compared with sham. However, incubation with the free radical scavenger, tempol, unmasked a significant increase in nitrite production by mTALs from STZ rats. Inhibition of PP2B attenuated the increase in nitrite production and NOS activity evident in mTALs from STZ rats. Analysis of specific NOS isoform activity revealed increased NOS1 and NOS2 activities in mTALs from STZ rats. All three NOS isoform activities were regulated in a PP2B-dependent manner. Western blot analysis detected no differences in NOS isoform expression, although phosphorylation of pThr 495 -NOS3 was significantly reduced in mTALs from STZ rats. Phosphorylation of pSer 852 -NOS1, pSer 633 -NOS3, and pSer 1177 -NOS3 was similar in mTALs from STZ and sham rats. Inhibition of PP2B did not alter the phosphorylation of NOS1 or NOS3 at known sites. In conclusion, while NO bioavailability in mTALs is reduced during diabetes, free radical scavenging with tempol unmasks increased NO production that involves PP2B-dependent activation of NOS1 and NOS2.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2009
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  • 9
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2017
    In:  Scientific Reports Vol. 7, No. 1 ( 2017-02-23)
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-02-23)
    Abstract: Endothelin-1 (ET-1) promotes renal damage during cardiovascular disease; yet, the molecular mechanisms involved remain unknown. Endoplasmic reticulum (ER) stress, triggered by unfolded protein accumulation in the ER, contributes to apoptosis and organ injury. These studies aimed to determine whether the ET-1 system promotes renal ER stress development in response to tunicamycin. ET B deficient (ET B def) or transgenic control (TG-con) rats were used in the presence or absence of ET A receptor antagonism. Tunicamycin treatment similarly increased cortical ER stress markers in both rat genotypes; however, only ET B def rats showed a 14–24 fold increase from baseline for medullary GRP78, sXBP-1, and CHOP. Pre-treatment of TG-con rats with the ET A blocker ABT-627 for 1 week prior to tunicamycin injection significantly reduced the ER stress response in cortex and medulla, and also inhibited renal apoptosis. Pre-treatment with ABT-627 failed to decrease renal ER stress and apoptosis in ET B def rats. In conclusion, the ET-1 system is important for the development of tunicamycin-induced renal ER stress and apoptosis. ET A receptor activation induces renal ER stress genes and apoptosis, while functional activation of the ET B receptor has protective effects. These results highlight targeting the ET A receptor as a therapeutic approach against ER stress-induced kidney injury.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2615211-3
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  • 10
    Online Resource
    Online Resource
    Elsevier BV ; 1992
    In:  Peptides Vol. 13, No. 6 ( 1992-11), p. 1181-1185
    In: Peptides, Elsevier BV, Vol. 13, No. 6 ( 1992-11), p. 1181-1185
    Type of Medium: Online Resource
    ISSN: 0196-9781
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1992
    detail.hit.zdb_id: 2019194-7
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