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  • 1
    Online Resource
    Online Resource
    Glomerular and tubular function during AT1 receptor blockade in pigs with neonatal induced partial ureteropelvic obstruction
    American Physiological Society ; 2007
    In:  American Journal of Physiology-Renal Physiology Vol. 292, No. 3 ( 2007-03), p. F921-F929
    Details
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 292, No. 3 ( 2007-03), p. F921-F929
    Abstract: Previously, we showed that neonatal induced chronic partial unilateral ureteral obstruction (PUUO) of the multipapillary pig kidney decreased glomerular filtration rate (GFR) of the obstructed kidney. We hypothesized that ANG II and nitric oxide (NO) are important for the changes in renal function and in the present study we examined the effects of chronic AT1 receptor blockade using CV-11974 (0.12 mg/h candesartan from age 23 to 30 days) on kidney function development after PUUO was induced in 2-day-old piglets. Moreover, the effect of superimposed acute NO inhibition using N G -nitro-l-arginine methyl ester (l-NAME; 15 mg/kg) was examined to identify if this has diagnostic potential. PUUO significantly increased GFR in the nonobstructed contralateral kidney independent of candesartan. In candesartan-treated piglets, the l-NAME-induced GFR reduction seen in normal and nonobstructed kidneys was absent in the partial obstructed kidneys. Urine output and fractional excretion of water were increased from the partial obstructed kidneys. Consistent with this immunohistochemical analyses showed a reduced aquaporin-2 labeling in the collecting duct principal cells. Moreover, renal sodium handling was compromised by PUUO evidenced by an increased fractional excretion of sodium which was enhanced by candesartan treatment. In conclusion, our findings suggest that the counterbalance between AT1 receptor-mediated vasoconstriction and NO-mediated vasodilatation which maintain GFR in normal young porcine kidneys is changed by neonatal induced chronic PUUO. This may have diagnostic potential in children with suspected congenital obstruction. Our results also demonstrate compromised tubular functions in response to chronic PUUO despite preservation of glomerular function.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    URL: Article
    DOI: 10.1152/ajprenal.00407.2006
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2007
    detail.hit.zdb_id: 1477287-5
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  • 2
    Online Resource
    Online Resource
    Both high and low maternal salt intake in pregnancy alter kidney development in the offspring
    American Physiological Society ; 2011
    In:  American Journal of Physiology-Renal Physiology Vol. 301, No. 2 ( 2011-08), p. F344-F354
    Details
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 301, No. 2 ( 2011-08), p. F344-F354
    Abstract: In humans, low glomerular numbers are related to hypertension, cardiovascular, and renal disease in adult life. The present study was designed 1) to explore whether above- or below-normal dietary salt intake during pregnancy influences nephron number and blood pressure in the offspring and 2) to identify potential mechanisms in kidney development modified by maternal sodium intake. Sprague-Dawley rats were fed low (0.07%)-, intermediate (0.51%)-, or high (3.0%)-sodium diets during pregnancy and lactation. The offspring were weaned at 4 wk and subsequently kept on a 0.51% sodium diet. The kidney structure was assessed at postnatal weeks 1 and 12 and the expression of proteins of interest at term and at week 1. Blood pressure was measured in male offspring by telemetry from postnatal month 2 to postnatal month 9. The numbers of glomeruli at weeks 1 and 12 were significantly lower and, in males, telemetrically measured mean arterial blood pressure after month 5 was higher in offspring of dams on a high- or low- compared with intermediate-sodium diet. A high-salt diet was paralleled by higher concentrations of marinobufagenin in the amniotic fluid and an increase in the expression of both sprouty-1 and glial cell-derived neutrophic factor in the offspring's kidney. The expression of FGF-10 was lower in offspring of dams on a low-sodium diet, and the expression of Pax-2 and FGF-2 was lower in offspring of dams on a high-sodium diet. Both excessively high and excessively low sodium intakes during pregnancy modify protein expression in offspring kidneys and reduce the final number of glomeruli, predisposing the risk of hypertension later in life.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    URL: Article
    DOI: 10.1152/ajprenal.00626.2010
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2011
    detail.hit.zdb_id: 1477287-5
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  • 3
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    Online Resource
    An unbiased stereological method for efficiently quantifying the innervation of the heart and other organs based on total length estimations
    American Physiological Society ; 2010
    In:  Journal of Applied Physiology Vol. 108, No. 5 ( 2010-05), p. 1402-1409
    Details
    In: Journal of Applied Physiology, American Physiological Society, Vol. 108, No. 5 ( 2010-05), p. 1402-1409
    Abstract: Quantitative information about the innervation is essential to analyze the structure-function relationships of organs. So far, there has been no unbiased stereological tool for this purpose. This study presents a new unbiased and efficient method to quantify the total length of axons in a given reference volume, illustrated on the left ventricle of the mouse heart. The method is based on the following steps: 1) estimation of the reference volume; 2) randomization of location and orientation using appropriate sampling techniques; 3) counting of nerve fiber profiles hit by a defined test area within an unbiased counting frame on paraffin sections stained immunohistochemically for protein gene product 9.5; 4) electron microscopic estimation of the mean number of axon profiles contained in one nerve fiber profile; 5) estimation of the degree of tissue shrinkage of specimens in paraffin; and 6) calculation of the total axon length within the reference volume, taking tissue shrinkage into account. In a set of five mouse hearts, the total length of axons ramifying between cardiomyocytes ranged between ∼50 and 100 m, with a mean of 75.98 m (SD 23.73). The time required for the microscopical analysis was ∼8 h/animal for an experienced observer. Using antibodies specific for different neuron subtypes and immunoelectron microscopy, this method is also suited to estimate the total axon length of neurons expressing different transmitters. This new and efficient method is particularly useful when structural remodeling takes place and is suspected to involve gain or loss of axons.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    URL: Article
    DOI: 10.1152/japplphysiol.01013.2009
    RVK:
    WA 15000
    RVK:
    XA 52094
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2010
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 4
    Online Resource
    Online Resource
    Estimation of the number of alveolar capillaries by the Euler number (Euler-Poincaré characteristic)
    American Physiological Society ; 2015
    In:  American Journal of Physiology-Lung Cellular and Molecular Physiology Vol. 309, No. 11 ( 2015-12-01), p. L1286-L1293
    Details
    In: American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 309, No. 11 ( 2015-12-01), p. L1286-L1293
    Abstract: The lung parenchyma provides a maximal surface area of blood-containing capillaries that are in close contact with a large surface area of the air-containing alveoli. Volume and surface area of capillaries are the classic stereological parameters to characterize the alveolar capillary network (ACN) and have provided essential structure-function information of the lung. When loss (rarefaction) or gain (angiogenesis) of capillaries occurs, these parameters may not be sufficient to provide mechanistic insight. Therefore, it would be desirable to estimate the number of capillaries, as it contains more distinct and mechanistically oriented information. Here, we present a new stereological method to estimate the number of capillary loops in the ACN. One advantage of this method is that it is independent of the shape, size, or distribution of the capillaries. We used consecutive, 1 μm-thick sections from epoxy resin-embedded material as a physical disector. The Euler-Poincaré characteristic of capillary networks can be estimated by counting the easily recognizable topological constellations of “islands,” “bridges,” and “holes.” The total number of capillary loops in the ACN can then be calculated from the Euler-Poincaré characteristic. With the use of the established estimator of alveolar number, it is possible to obtain the mean number of capillary loops per alveolus. In conclusion, estimation of alveolar capillaries by design-based stereology is an efficient and unbiased method to characterize the ACN and may be particularly useful for studies on emphysema, pulmonary hypertension, or lung development.
    Type of Medium: Online Resource
    ISSN: 1040-0605 , 1522-1504
    URL: Article
    DOI: 10.1152/ajplung.00410.2014
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2015
    detail.hit.zdb_id: 1477300-4
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    AT 1 receptor blockade prevents interstitial and glomerular apoptosis but not fibrosis in pigs with neonatal induced partial unilateral ureteral obstruction
    American Physiological Society ; 2007
    In:  American Journal of Physiology-Renal Physiology Vol. 292, No. 6 ( 2007-06), p. F1771-F1781
    Details
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 292, No. 6 ( 2007-06), p. F1771-F1781
    Abstract: Obstruction-induced fibrosis is a leading cause of end-stage renal failure in children. The pathophysiological mechanisms may involve apoptosis and the renin-angiotensin system. We studied apoptosis and fibrosis in a well-established neonatal pig model with unilateral partial ureteral obstruction (PUUO) induced during ongoing nephrogenesis in 2-day-old piglets. The role of angiotensin II (ANG II) was studied using the AT 1 receptor blocker CV-11974 (0.12 mg/h candesartan from age 23 to 30 days). At day 30 the kidneys were perfusion fixed and fibrosis, apoptosis, and tubular lengths were quantitated using stereological methods, picro Sirius red staining, and immunohistochemical techniques identifying activated caspase 3, aquaporin-2 (AQP2), and von Willebrand factor. The collagen content was assessed by hydroxyproline density. Neonatal induced PUUO increased interstitial and glomerular cell apoptosis and fibrosis. At this stage, PUUO did not increase tubular cell apoptosis or decrease tubular length and cell number. AT 1 receptor blockade prevented the PUUO-induced interstitial and glomerular cell apoptosis but did not attenuate fibrosis. In conclusion, AT 1 receptor blockade after the end of nephrogenesis may prevent interstitial and glomerular cell apoptosis but not fibrosis, suggesting that pathways not involving AT 1 receptor stimulation contribute to neonatal obstruction-induced fibrosis or that prevention of interstitial cell apoptosis counteracts a potential antifibrotic effect of AT 1 receptor blockade in this pig model of congenital obstructive nephropathy. Our results demonstrate that ANG II plays a role in PUUO-induced glomerular cell apoptosis.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    URL: Article
    DOI: 10.1152/ajprenal.00479.2006
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2007
    detail.hit.zdb_id: 1477287-5
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