Distal Tubular Feedback Control of Renal Hemodynamics and Autoregulation

Navar, L. G.; Ploth, David W.; Bell, P. Darwin

doi:10.1146/annurev.ph.42.030180.003013

Cited by 49 publications

(20 citation statements)

References 39 publications

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“…These hemodynamic adjustments to acute Nx were central to glomerular hyperfiltration and occurred notwithstanding a marked rise in distal tubular fluid flow (6). Based on the tubuloglomerular feedback hypothesis of renal autoregulation which predicts that increased distal tubular fluid flow (or some component thereof) should cause afferent arteriole constriction and therefore a reduction in PG (7)(8)(9), our data suggest that renal autoregulation and in particular the autoregulatory capacity of the remnant nephrons for PG appears to be either reset or lost after acute Nx. Previous work on renal autoregulation in experimental models ofCRF have been limited to investigations at the whole kidney level in the chronic state.…”

Section: Introductionmentioning

confidence: 60%

“…Taken together, these results suggest that in the pathological condition of acute nephron loss, the autoregulatory capacity for PG is significantly impaired in Nx glomeruli. The defect or defects that may explain the substantial loss of autoregulation of PG in this model are presently unknown and might reside in the myogenic mechanism (21) and/or in a single component or a combination of the three components ofthe tubuloglomerular feedback mechanism (i.e., signal, sensor, and effector sites) (7)(8)(9). Although the findings presented above do not permit a determination as to which component(s) is altered, based on our previous study in which we documented that a 45% reduction in afferent arteriolar resistance was the mechanism to account entirely for the observed glomerular hypertension and hyperperfusion, and therefore glomerular hyperfiltration 24 h after Nx (6), one could speculate that a lack of responsiveness at this afferent vascular effector site may be the critical alteration.…”

Section: Discussionmentioning

confidence: 99%

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Impaired autoregulation of glomerular capillary hydrostatic pressure in the rat remnant nephron.

Pelayo¹,

Westcott²

1991

J. Clin. Invest.

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In the present micropuncture study, the autoregulation of glomerular capillary hydrostatic pressure (PG) in Munich-Wistar rats 24 h after 75% nephrectomy (Nx) or sham operation (Sh) was investigated. The effect of varying renal perfusion pressure (RPP) on paired determinations of directly measured PG was evaluated in glomeruli ofnephrons in which distal fluid delivery was present (unblocked). Autoregulation of PG in Sh glomeruli with unblocked tubules occurred at RPP values between 99.5±1.0 and 132.1±1.0 mmHg. In contrast, in Nx glomeruli with unblocked tubules PG increased by 0.32±0.07 mmHg/ mmHg increase in RPP over this same range of RPP (P < 0.0001). To determine whether enhanced prostaglandins synthesis was responsible for the altered regulation of PG in Nx glomeruli, we repeated the micropuncture measurements in a setting of prostaglandin synthesis inhibition. Although prostaglandins synthesis inhibition did not affect the autoregulation ofPG in Sh glomeruli, it did normalize the autoregulatory capacity for PG of Nx glomeruli with unblocked tubules. Thus, acute Nx is associated with a significant loss of the autoregulatory capacity for PG and this impairment appears to be related to a prostaglandin-mediated alteration of the responsiveness of the vascular effector site for autoregulation. (J. Clin. Invest. 1991.

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Section: Introductionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Impaired autoregulation of glomerular capillary hydrostatic pressure in the rat remnant nephron.

Pelayo¹,

Westcott²

1991

J. Clin. Invest.

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“…At this point, there is a plaque of very specialized and differentiated cells in the distal tubule known as the macula densa ( Figure 6B). The macula densa detects changes in the distal tubular fluid composition and transmits signals to the adjacent extraglomerular mesangial cells and afferent arterioles (47)(48)(49)(50)(51)(52)(53). Extraglomerular mesangial cells are anatomically in continuity with the glomerular mesangial cells and transmit the signal from the macula densa to the glomeru- lus.…”

Section: Discussionmentioning

confidence: 99%

Loss of the BMP antagonist USAG-1 ameliorates disease in a mouse model of the progressive hereditary kidney disease Alport syndrome

Tanaka¹,

Asada²,

Higashi³

et al. 2010

J. Clin. Invest.

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The glomerular basement membrane (GBM) is a key component of the filtering unit in the kidney. Mutations involving any of the collagen IV genes (COL4A3, COL4A4, and COL4A5) affect GBM assembly and cause Alport syndrome, a progressive hereditary kidney disease with no definitive therapy. Previously, we have demonstrated that the bone morphogenetic protein (BMP) antagonist uterine sensitization-associated gene-1 (USAG-1) negatively regulates the renoprotective action of BMP-7 in a mouse model of tubular injury during acute renal failure. Here, we investigated the role of USAG-1 in renal function in Col4a3 -/-mice, which model Alport syndrome. Ablation of Usag1 in Col4a3 -/-mice led to substantial attenuation of disease progression, normalization of GBM ultrastructure, preservation of renal function, and extension of life span. Immunohistochemical analysis revealed that USAG-1 and BMP-7 colocalized in the macula densa in the distal tubules, lying in direct contact with glomerular mesangial cells. Furthermore, in cultured mesangial cells, BMP-7 attenuated and USAG-1 enhanced the expression of MMP-12, a protease that may contribute to GBM degradation. These data suggest that the pathogenetic role of USAG-1 in Col4a3 -/-mice might involve crosstalk between kidney tubules and the glomerulus and that inhibition of USAG-1 may be a promising therapeutic approach for the treatment of Alport syndrome.

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“…All in the JEG cells could represent the crucial linking substance ofthe tubulo-glomerular feedback mechanism. The hypothesis (33)(34)(35)(36) postulates that the composition of the distal tubular fluid influences the resistance in the glomerular arterioles, thereby regulating the filtration rate in the glomerulus. All preformed in the JEG cells could rapidly modify the width of the glomerular vessels by two different mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II immunoreactivity coexists with renin in the juxtaglomerular granular cells of the kidney.

Celio¹,

Inagami²

1981

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

109

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The multiple physiologic functions ofangiotensin H (All) are generally supposed to be mediated by the peptide generated in the blood circulation. In addition to this extracellular mechanism of AII formation, we have obtained immunohistochemical evidence for the intracellular synthesis ofAll in the kidney. Rats were perfused with fixative, and paraffin sections of the kidneys were processed with antisera against renin (EC 3.4.99.19), AII, and other components ofthe renin-angiotensin system. Renin immunoreactivity was regularly observed in the epithelioid granular cells in the media ofthe afferent vessel ofthe glomerulus. All immunoreactivity was found to coexist within the same cells. This observation points to an intracellular production of All in the juxtaglomerular epithelioid granular cells. AUl may then be released concomitantly with renin in the interstitial fluid and in the blood. The paracrine secretion of All could exert a local regulatory influence on the tonus of the glomerular vessels.

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Distal Tubular Feedback Control of Renal Hemodynamics and Autoregulation

Cited by 49 publications

References 39 publications

Impaired autoregulation of glomerular capillary hydrostatic pressure in the rat remnant nephron.

Impaired autoregulation of glomerular capillary hydrostatic pressure in the rat remnant nephron.

Loss of the BMP antagonist USAG-1 ameliorates disease in a mouse model of the progressive hereditary kidney disease Alport syndrome

Angiotensin II immunoreactivity coexists with renin in the juxtaglomerular granular cells of the kidney.

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