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Role of connecting tubule glomerular feedback in obesity related renal damage.
- Source :
-
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2018 Dec 01; Vol. 315 (6), pp. F1708-F1713. Date of Electronic Publication: 2018 Oct 10. - Publication Year :
- 2018
-
Abstract
- Zucker obese rats (ZOR) have higher glomerular capillary pressure (P <subscript>GC</subscript> ) that can cause renal damage. P <subscript>GC</subscript> is controlled by afferent (Af-Art) and efferent arteriole (Ef-Art) resistance. Af-Art resistance is regulated by factors that regulate other arterioles, such as myogenic response. In addition, it is also regulated by 2 intrinsic feedback mechanisms: 1) tubuloglomerular feedback (TGF) that causes Af-Art constriction in response to increased NaCl in the macula densa and 2) connecting tubule glomerular feedback (CTGF) that causes Af-Art dilatation in response to an increase in NaCl transport in the connecting tubule via the epithelial sodium channel. Since CTGF is an Af-Art dilatory mechanism, we hypothesized that increased CTGF contributes to TGF attenuation, which in turn increases P <subscript>GC</subscript> in ZOR. We performed a renal micropuncture experiment and measured stop-flow pressure (P <subscript>SF</subscript> ), which is an indirect measurement of P <subscript>GC</subscript> in ZOR. Maximal TGF response at 40 nl/min was attenuated in ZOR (4.47 ± 0.60 mmHg) in comparison to the Zucker lean rats (ZLR; 8.54 ± 0.73 mmHg, P < 0.05), and CTGF was elevated in ZOR (5.34 ± 0.87 mmHg) compared with ZLR (1.12 ± 1.28 mmHg, P < 0.05). CTGF inhibition with epithelial sodium channel blocker normalized the maximum P <subscript>SF</subscript> change in ZOR indicating that CTGF plays a significant role in TGF attenuation (ZOR, 10.67 ± 1.07 mmHg vs. ZLR, 9.5 ± 1.53 mmHg). We conclude that enhanced CTGF contributes to TGF attenuation in ZOR and potentially contribute to progressive renal damage.
- Subjects :
- Animals
Arterial Pressure
Disease Models, Animal
Feedback, Physiological
Glomerular Filtration Rate
Kidney Diseases metabolism
Kidney Diseases pathology
Kidney Diseases physiopathology
Kidney Glomerulus metabolism
Kidney Glomerulus pathology
Kidney Tubules pathology
Kidney Tubules physiopathology
Proteinuria metabolism
Proteinuria pathology
Proteinuria physiopathology
Rats, Zucker
Signal Transduction
Up-Regulation
Connective Tissue Growth Factor metabolism
Kidney Diseases etiology
Kidney Glomerulus blood supply
Kidney Tubules metabolism
Microcirculation
Obesity complications
Proteinuria etiology
Renal Circulation
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1466
- Volume :
- 315
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Renal physiology
- Publication Type :
- Academic Journal
- Accession number :
- 30303713
- Full Text :
- https://doi.org/10.1152/ajprenal.00227.2018