Increased Hyaluronic Acid in the Inner Renal Medulla of Obese Dogs
Abstract
Abstract Dogs placed on a high-fat diet develop obesity and hypertension associated with marked sodium retention that is due to increased tubular reabsorption. Previous studies showed that renal interstitial hydrostatic pressure is elevated in obese dogs compared with lean dogs, and histological studies revealed increases in medullary interstitial cells and expansion of the medullary but not the cortical extracellular matrix. This matrix stained intensively with Alcian Blue at pH 2.6, colloidal iron, and periodic acid–Schiff, suggesting increased glycosaminoglycans. The goal of this study was to quantitate medullary glycosaminoglycan content in obese (n=8) compared with lean (n=8) dogs. Measurement of total glycosaminoglycan content, estimated from uronic acid content, and of hyaluronate, the most abundant glycosaminoglycan in canine renal medulla, with an enzyme-linked immunosorbent assay indicated that there were no significant differences in total glycosaminoglycan or hyaluronate contents in the outer medulla of obese dogs compared with those in lean dogs. In contrast, in the inner medulla of obese dogs there was a 140% increase in hyaluronate compared with the content in lean dogs (4.3±0.5 versus 1.8±0.2 mg hyaluronate per gram wet tissue, respectively; P <.05); however, total glycosaminoglycan content was not significantly different (6.9±0.7 versus 6.2±0.5 mg uronic acid per gram wet tissue) in obese and lean dogs. These results suggest a change in the relative proportion of the glycosaminoglycan species in the inner medulla of obese dogs, with a selective increase in hyaluronate. These changes in extracellular matrix could contribute to the altered intrarenal physical forces, tubular compression, and increased tubular reabsorption observed in obese dogs.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In obese rabbits, dogs and humans, the levels of renal medullary glycosaminoglycans, especially hyaluronan, were markedly elevated compared with lean controls.
“In obese rabbits, dogs and humans, the levels of renal medullary glycosaminoglycans, especially hyaluronan, which is an important component of the ECM and is often associated with tissue inflammation and oedema, were markedly elevated compared with lean controls53–55.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [54]
Cites
A modified uronic acid carbazole reaction
Bitter, T., & Muir, H. M. (1962) · Analytical Biochemistry · doi:10.1016/0003-2697(62)90095-7 · Cited by 6,239 · see citing works
Reisin, E., Abel, R., Modan, M., Silverberg, D. S., Eliahou, H. E., & Modan, B. (1978) · New England Journal of Medicine · doi:10.1056/nejm197801052980101 · Cited by 759 · see citing works
Stamler, R. (1978) · JAMA · doi:10.1001/jama.240.15.1607 · Cited by 712 · see citing works
Chiang, B. N., Perlman, L. V., & Epstein, F. H. (1969) · Circulation · doi:10.1161/01.cir.39.3.403 · Cited by 579 · see citing works
Obesity-induced hypertension. Renal function and systemic hemodynamics.
Hall, J. E., Brands, M. W., Dixon, W. N., & Smith, M. J. (1993) · Hypertension · doi:10.1161/01.hyp.22.3.292 · Cited by 328 · see citing works
Self-citationHavlik, R. J., Hubert, H. B., FABSITZ, R. R., & Feinleib, M. (1983) · Annals of Internal Medicine · doi:10.7326/0003-4819-98-5-855 · Cited by 206 · see citing works
Louis K. Dahl Memorial Lecture. Renal and cardiovascular mechanisms of hypertension in obesity.
Hall, J. E. (1994) · Hypertension · doi:10.1161/01.hyp.23.3.381 · Cited by 204 · see citing works
Self-citationAbnormal pressure natriuresis. A cause or a consequence of hypertension?
Hall, J. E., Mizelle, H. L., Hildebrandt, D. A., & Brands, M. W. (1990) · Hypertension · doi:10.1161/01.hyp.15.6.547 · Cited by 193 · see citing works
Self-citationBlood pressure and hormone changes associated with weight reduction in the obese.
Sowers, J. R., Nyby, M. D., Stern, N., Beck, F. W., Baron, S. H., Catania, R. A., & Vlachis, N. (1982) · Hypertension · doi:10.1161/01.hyp.4.5.686 · Cited by 164 · see citing works
Renal interstitial pressure and sodium excretion during renal vein constriction
Burnett, J. C. J., & Knox, F. G. (1980) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1980.238.4.f279 · Cited by 141 · see citing works
[21] Proteoglycans: Isolation and purification from tissue cultures
Yanagishita, M., Midura, R. J., & Hascall, V. (1987) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(87)38023-1 · Cited by 115 · see citing works
Pathogenesis of weight-related changes in blood pressure in dogs.
Rocchini, A. P., Moorehead, C., DeRemer, S. J., & Bondie, D. (1989) · Hypertension · doi:10.1161/01.hyp.13.6.922 · Cited by 110 · see citing works
Mechanisms of Hypertension Associated with Obesity
Dustan, H. P. (1983) · Annals of Internal Medicine · doi:10.7326/0003-4819-98-5-860 · Cited by 110 · see citing works
Obesity-induced hypertension in the dog.
Rocchini, A. P., Moorehead, C., Wentz, E., & DeRemer, S. J. (1987) · Hypertension · doi:10.1161/01.hyp.9.6_pt_2.iii64 · Cited by 90 · see citing works
Effects of membrane potential on electrical slow waves of canine proximal colon
Smith, T. K., Reed, J. B., & Sanders, K. M. (1988) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1988.255.6.c828 · Cited by 74 · see citing works
THE EFFECT OF WEIGHT REDUCTION UPON THE BLOOD-PRESSURE OF OBESE HYPERTENSIVE WOMEN
Fletcher, A. P. (1954) · QJM · doi:10.1093/oxfordjournals.qjmed.a066706 · Cited by 64 · see citing works
GOLDBERG, R. L. (1988) · Analytical Biochemistry · doi:10.1016/0003-2697(88)90043-7 · Cited by 49 · see citing works
Regional distribution of acid mucopolysaccharides in the kidney
Castor, C. W., & Greene, J. A. (1968) · Journal of Clinical Investigation · doi:10.1172/jci105898 · Cited by 48 · see citing works
Effect of direct increases in renal interstitial hydrostatic pressure on sodium excretion
Granger, J. P., Haas, J. A., Pawłowska, D., & Knox, F. G. (1988) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1988.254.4.f527 · Cited by 42 · see citing works
Mechanisms of hypertension in obesity
López de Fez, C. M., Gaztelu, M. T., Rubio, T., & Castaño, A. (2008) · Anales del Sistema Sanitario de Navarra · doi:10.23938/assn.0475 · Cited by 38 · see citing works
Segmental analysis of sodium reabsorption during renal vein constriction
Burnett, J. C. J., Haas, J. A., & Knox, F. G. (1982) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1982.243.1.f19 · Cited by 38 · see citing works
Effects of renal artery pressure on interstitial pressure and Na excretion during renal vasodilation
Granger, J. P., & Scott, J. W. (1988) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1988.255.5.f828 · Cited by 27 · see citing works
Pressure-flow relationships in Henle's loops and long collapsible rubber tubes
Koh, Y. G., & Baines, A. D. (1974) · Kidney International · doi:10.1038/ki.1974.4 · Cited by 14 · see citing works
Flagged first, then by citations
1 of the 24 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms
Hall, J. E., do Carmo, J. M., da Silva, A. A., Wang, Z., & Hall, M. E. (2015) · Circulation Research · doi:10.1161/circresaha.116.305697 · Cited by 1,360 · see citing works
Self-citationObesity-related glomerulopathy: An emerging epidemic
Kambham, N., Markowitz, G. S., Valeri, A. M., Lin, J., & D’Agati, V. D. (2001) · Kidney International · doi:10.1046/j.1523-1755.2001.0590041498.x · Cited by 1,279 · see citing works
Glomerular hyperfiltration in diabetes: mechanisms, clinical significance, and treatment
Tonneijck, L., Muskiet, M. H. A., Smits, M. M., van Bommel, E. J., Heerspink, H. J. L., van Raalte, D. H., & Joles, J. A. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2016060666 · Cited by 887 · see citing works
The Kidney, Hypertension, and Obesity
Hall, J. E. (2003) · Hypertension · doi:10.1161/01.hyp.0000052314.95497.78 · Cited by 868 · see citing works
Self-citationObesity, kidney dysfunction and hypertension: mechanistic links
Hall, J. E., do Carmo, J. M., da Silva, A. A., Wang, Z., & Hall, M. E. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0145-4 · Cited by 654 · see citing works
Self-citationFunctional and Structural Changes in the Kidney in the Early Stages of Obesity
HENEGAR, J. R., BIGLER, S. A., HENEGAR, L. K., TYAGI, S. C., & HALL, J. E. (2001) · Journal of the American Society of Nephrology · doi:10.1681/asn.v1261211 · Cited by 549 · see citing works
Self-citationObesity, hypertension, and chronic kidney disease
Hall, J., Juncos, L., Wang, Z., Hall, M., do Carmo, J., & da Silva, A. (2014) · International Journal of Nephrology and Renovascular Disease · doi:10.2147/ijnrd.s39739 · Cited by 520 · see citing works
Self-citationMontani, J.-P., Carroll, J. F., Dwyer, T. M., Antic, V., Yang, Z., & Dulloo, A. G. (2004) · International Journal of Obesity · doi:10.1038/sj.ijo.0802858 · Cited by 294 · see citing works
Self-citationMechanisms of Hypertension and Kidney Disease in Obesity
HALL, J. E., BRANDS, M. W., & HENEGAR, J. R. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb07788.x · Cited by 222 · see citing works
Self-citationMechanisms of Abnormal Renal Sodium Handling in Obesity Hypertension
Hall, J. (1997) · American Journal of Hypertension · doi:10.1016/s0895-7061(97)00075-7 · Cited by 213 · see citing works
Self-citationPathophysiology of obesity hypertension
Hall, J. E. (2000) · Current Hypertension Reports · doi:10.1007/s11906-000-0073-4 · Cited by 185 · see citing works
Self-citationAssociation of metabolic syndrome and chronic kidney disease
Scurt, F. G., Ganz, M. J., Herzog, C., Bose, K., Mertens, P. R., & Chatzikyrkou, C. (2024) · Obesity Reviews · doi:10.1111/obr.13649 · Cited by 155 · see citing works
Is There a Rationale for Angiotensin Blockade in the Management of Obesity Hypertension?
Sharma, A. M. (2004) · Hypertension · doi:10.1161/01.hyp.0000132568.71409.a2 · Cited by 136 · see citing works
ABNORMAL KIDNEY FUNCTION AS A CAUSE AND A CONSEQUENCE OF OBESITY HYPERTENSION
Hall, J. E., Brands, M. W., Henegar, J. R., & Shek, E. W. (1998) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.1998.tb02146.x · Cited by 108 · see citing works
Self-citationHsueh, W. A., & Buchanan, T. A. (1994) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(18)30105-1 · Cited by 91 · see citing works
El-Atat, F. A., Aneja, A., McFarlane, S. I., & Sowers, J. R. (2003) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(03)00070-7 · Cited by 82 · see citing works
Distribution of renal medullary hyaluronan in lean and obese rabbits
Dwyer, T. M., Banks, S. A., Alonso-Galicia, M., Cockrell, K., Carroll, J. F., Bigler, S. A., & Hall, J. E. (2000) · Kidney International · doi:10.1046/j.1523-1755.2000.00218.x · Cited by 68 · see citing works
Self-citationKim, N. H., & Kim, N. H. (2022) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2022.0209 · Cited by 49 · see citing works
Martin, W. P., White, J. P., López-Hernández, F. J., Docherty, N. G., & le Roux, C. W. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00289 · Cited by 48 · see citing works
The roles of hyaluronan in kidney development, physiology and disease
Rabelink, T. J., Wang, G., van der Vlag, J., & van den Berg, B. M. (2024) · Nature Reviews Nephrology · doi:10.1038/s41581-024-00883-5 · Cited by 34 · see citing works
Özbek, L., Abdel‐Rahman, S. M., Unlu, S., Güldan, M., Copur, S., Burlacu, A., Covic, A. C., & Kanbay, M. (2024) · Medicina · doi:10.3390/medicina60101668 · Cited by 22 · see citing works
Obesity in dogs: Effects on renal function, blood pressure, and renal disease
Joles, J. A. (1998) · Veterinary Quarterly · doi:10.1080/01652176.1998.9694854 · Cited by 15 · see citing works
Myo-inositol oxygenase accentuates renal tubular injury initiated by endoplasmic reticulum stress
Tominaga, T., Sharma, I., Fujita, Y., Doi, T., Wallner, A. K., & Kanwar, Y. S. (2018) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00534.2018 · Cited by 15 · see citing works
Altered responsiveness of the kidney to activation of the renal nerves in fat-fed rabbits
Michaels, S., Eppel, G. A., Burke, S. L., Head, G. A., Armitage, J. A., Carroll, J. F., Malpas, S. C., & Evans, R. G. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90931.2008 · Cited by 11 · see citing works
The renin-angiotensin system in obesity hypertension
Sharma, A. M., & Engeli, S. (2001) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.1177/14703203010020012001 · Cited by 7 · see citing works
Heerspink, H. J. L., van Raalte, D. H., Bjornstad, P., Bunck, M. C. M., Wu, P., Tunali, I., Miličević, Z., & Koeneman, L. (2025) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfaf230 · Cited by 5 · see citing works
Obesity, Fatty Kidney, and Hypertension: Potential Role of Aldosterone
Hall, M. E., Omoto, A. C. M., & Hall, J. E. (2025) · Hypertension · doi:10.1161/hypertensionaha.125.25627 · Cited by 5 · see citing works
Self-citationAnimal Models of Diabetic Kidney Disease
Nguyen, I., van Koppen, A., & Joles, J. A. (2018) · Springer eBooks · doi:10.1007/978-3-319-93521-8_23 · Cited by 4 · see citing works
Kolatkar, N. S., Thomas, A., & Williams, G. H. (2006) · Fundamental and clinical cardiology · doi:10.3109/9781420018905.002 · Cited by 2 · see citing works
Metabolisches Syndrom und Nierenkrankheiten
Ganz, M. J., Bender, S. T., Gross, C., Bose, K., Mertens, P. R., & Scurt, F. G. (2022) · Die Nephrologie · doi:10.1007/s11560-022-00595-6 · Cited by 1 · see citing works
Obesity, insulin resistance, and the renal circulation
Hall, J. E., Brands, M. W., Shek, E. W., & Henegar, J. R. (2000) · Advances in organ biology · doi:10.1016/s1569-2590(00)09076-5
Self-citationZhang, X., Ren, X., Chang, X., Liu, J., & Wang, G. (2025) · BMC Nephrology · doi:10.1186/s12882-025-04474-9
- Authors
- Alonso-Galicia, M., Dwyer, T. M., Herrera, G. A., & Hall, J. E.
- Affiliations
- From the Department of Physiology and Biophysics (M.A.-G., T.M.D., J.E.H.), University of Mississippi Medical Center, Jackson, and the Department of Surgical Pathology (G.A.H.), University of Alabama at Birmingham.
- University of Mississippi Medical Center (US)
- ORCID
- Hall, John E.
- Venue
- Hypertension
- Published
- 1995-04
- Volume
- 25
- Issue
- 4
- Pages
- 888-892
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W1967902501
- Cited by
- 32
- References
- 24
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 1 · 2022: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 1 · 2015: 1 · 2014: 1
- FWCI
- 0.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl023502-13, 5r01hl039399-05)
- National Heart, Lung, and Blood Institute (HL-23502, HL‐51971, HL-39399, P01HL051971)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Health Sciences › Veterinary › Small Animals › Veterinary Medicine and Surgery
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- hyaluronic acid, renal medulla, obesity, glycosaminoglycans, uronic acid, high-fat diet, dogs, sodium retention, tubular reabsorption, extracellular matrix, inner medulla
- MeSH terms
- Animals, Dogs, Hyaluronic Acid, Kidney Medulla, Obesity, Reference Values, Uronic Acids
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review