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Oscar A Carretero - One of the best experts on this subject based on the ideXlab platform.

  • role of connecting tubule Glomerular feedback in obesity related renal damage
    American Journal of Physiology-renal Physiology, 2018
    Co-Authors: Sumit R. Monu, Mani Maheshwari, Edward L. Peterson, Oscar A Carretero
    Abstract:

    Zucker obese rats (ZOR) have higher Glomerular Capillary Pressure (PGC) that can cause renal damage. PGC is controlled by afferent (Af-Art) and efferent arteriole (Ef-Art) resistance. Af-Art resist...

  • connecting tubule Glomerular feedback mediates tubuloGlomerular feedback resetting after unilateral nephrectomy
    American Journal of Physiology-renal Physiology, 2018
    Co-Authors: Sumit R. Monu, Kristopher Kutskill, J X Masjoanjuncos, Edward L. Peterson, Nitin Kumar, Hong Wang, Oscar A Carretero
    Abstract:

    Unilaterally nephrectomized rats (UNx) have higher Glomerular Capillary Pressure (PGC) that can cause significant Glomerular injury in the remnant kidney. PGC is controlled by the ratio of afferent...

  • abstract 066 regulation of nephron afferent arteriole resistance in obesity role of insulin and connecting tubule Glomerular feedback
    Hypertension, 2017
    Co-Authors: Sumit R. Monu, Mani Maheshwari, E. L. Peterson, Oscar A Carretero
    Abstract:

    Introduction: In obesity, increased Glomerular Capillary Pressure (PGC) may participate in renal damage.PGC is controlled in part by afferent arteriolar (Af-Art) resistance that in turn is regulate...

  • Pressure-Induced Constriction of the Afferent Arteriole of Spontaneously Hypertensive Rats
    2016
    Co-Authors: Sadayoshi Ito, Luis A. Juncos, Oscar A Carretero
    Abstract:

    In uncomplicated essential hypertension, renal blood flow, Glomerular filtration rate, and Glomerular Capillary Pressure are within the normal range despite elevated renal perfusion Pressure, suggesting abnormally high resistance of the preGlomerular vessels. Among various preGlomerular vascular segments, the afferent arteriole (Af-Art) is thought to be the site responsible for most resistance. However, little is known about the vascular reactivity of the Af-Art or its alteration in hypertension. In this study, we tested the hypothesis that Pressure-induced constriction is exaggerated in Af-Arts from spontaneously hypertensive rats (SHRs). Single Af-Arts were microdissected from kidneys of SHRs and normotensive control Wistar-Kyoto (WKY) rats and were microperfused in vitro. When Pressure in the Af-Art was increased stepwise from 20 to 80 mm Hg, luminal diameter increased similarly in both WKY and SHR Af-Arts (from 10.0±0.8 to 18.6±1J fim and from 10.1±L2 to 16.9±L5 /xm, respectively). However, when Pressure was further increased to 140 mm Hg, the diameter remained unchanged in WKY Af-Arts (19.2±1.9 /*m), whereas it decreased significantly to l l. l±0.9 /un in those from SHRs. We conclude that Pressure-induced constriction is exaggerated in SHR Af-Arts, which may contribute to the development and maintenance of hypertension. (Hyper

  • abstract 118 role of connecting tubule Glomerular feedback in tubuloGlomerular feedback resetting after unilateral nephrectomy
    Hypertension, 2015
    Co-Authors: Sumit R. Monu, Branislava Janic, Kristopher Kutskill, Cesar A Romero, J. X. Masjoan Juncos, Ed Peterson, Jeffrey L. Garvin, Hong Wang, Oscar A Carretero
    Abstract:

    TubuloGlomerular feedback (TGF) and connecting tubule Glomerular feedback (CTGF) autoregulate nephronal afferent arteriolar resistance. In TGF, the macula densa signals the afferent arteriole to constrict when NaCl transport is enhanced by increased luminal NaCl, via sodium[[Unable to Display Character: –]]potassium-2-chloride cotransporter-2 (NKCC2). CTGF is mediated by connecting tubule sodium transport via epithelial sodium channel (ENaC) and dilates the afferent arteriole. Attenuation or resetting of TGF occurs after unilateral nephrectomy (UNX), but the mechanism behind this resetting remains unclear. This TGF resetting after UNX has been implicated in progressive Glomerular damage due to sustained increase in Glomerular Capillary Pressure. Since TGF is attenuated after UNX, we sought to test the hypothesis that CTGF is enhanced and that it contributes to TGF resetting after UNX. To test this hypothesis, we performed right side UNX in Sprague Dawley (SD) rats. 24 hours after surgery, we performed micropuncture of individual rat nephrons while measuring stop-flow Pressure (PSF), which is an index of Glomerular Capillary Pressure and afferent arteriolar tone. PSF decreases with an increase in afferent arteriolar tone. TGF response was measured as a decrease in PSF induced by switching late proximal perfusion from 0,10,20,30 and 40nl/min. Maximal TGF response was 1.3 ± 1.7 mmHg in UNX rats while 8.2 ± 0.9 mmHg in sham-UNX rats indicating a TGF resetting in UNX rats. When CTGF was inhibited with the ENaC blocker Benzamil (1μM), TGF response was 10±1.2 mmHg in UNX rats and 14.8± 1.3 mmHg in sham-UNX rats, indicating the restoration of TGF responses in UNX. We conclude that enhanced CTGF contributes to the TGF resetting after 24 hours of UNX. Enhanced CTGF may be responsible for Glomerular damage post UNX.

Jeffrey L. Garvin - One of the best experts on this subject based on the ideXlab platform.

  • abstract 118 role of connecting tubule Glomerular feedback in tubuloGlomerular feedback resetting after unilateral nephrectomy
    Hypertension, 2015
    Co-Authors: Sumit R. Monu, Branislava Janic, Kristopher Kutskill, Cesar A Romero, J. X. Masjoan Juncos, Ed Peterson, Jeffrey L. Garvin, Hong Wang, Oscar A Carretero
    Abstract:

    TubuloGlomerular feedback (TGF) and connecting tubule Glomerular feedback (CTGF) autoregulate nephronal afferent arteriolar resistance. In TGF, the macula densa signals the afferent arteriole to constrict when NaCl transport is enhanced by increased luminal NaCl, via sodium[[Unable to Display Character: –]]potassium-2-chloride cotransporter-2 (NKCC2). CTGF is mediated by connecting tubule sodium transport via epithelial sodium channel (ENaC) and dilates the afferent arteriole. Attenuation or resetting of TGF occurs after unilateral nephrectomy (UNX), but the mechanism behind this resetting remains unclear. This TGF resetting after UNX has been implicated in progressive Glomerular damage due to sustained increase in Glomerular Capillary Pressure. Since TGF is attenuated after UNX, we sought to test the hypothesis that CTGF is enhanced and that it contributes to TGF resetting after UNX. To test this hypothesis, we performed right side UNX in Sprague Dawley (SD) rats. 24 hours after surgery, we performed micropuncture of individual rat nephrons while measuring stop-flow Pressure (PSF), which is an index of Glomerular Capillary Pressure and afferent arteriolar tone. PSF decreases with an increase in afferent arteriolar tone. TGF response was measured as a decrease in PSF induced by switching late proximal perfusion from 0,10,20,30 and 40nl/min. Maximal TGF response was 1.3 ± 1.7 mmHg in UNX rats while 8.2 ± 0.9 mmHg in sham-UNX rats indicating a TGF resetting in UNX rats. When CTGF was inhibited with the ENaC blocker Benzamil (1μM), TGF response was 10±1.2 mmHg in UNX rats and 14.8± 1.3 mmHg in sham-UNX rats, indicating the restoration of TGF responses in UNX. We conclude that enhanced CTGF contributes to the TGF resetting after 24 hours of UNX. Enhanced CTGF may be responsible for Glomerular damage post UNX.

  • mechanism of impaired afferent arteriole myogenic response in dahl salt sensitive rats role of 20 hete
    American Journal of Physiology-renal Physiology, 2014
    Co-Authors: Martin A Dambrosio, Edward L. Peterson, Jeffrey L. Garvin, Oscar A Carretero
    Abstract:

    The afferent arteriole (Af-Art) controls Glomerular Capillary Pressure, an important determinant of Glomerular injury. Af-Art myogenic response is mediated by ATP, and ATP signaling is in turn mediated by 20-HETE. Dahl salt-sensitive rats (Dahl SS) have decreased renal 20-HETE production. We hypothesized that Dahl SS have an impaired myogenic response and constrictor response to ATP, due to decreased 20-HETE. Af-Arts from Dahl SS or Dahl salt-resistant rats (Dahl SR) were microdissected and perfused. When myogenic response was induced by increasing Af-Art perfusion Pressure from 60 to 140 mmHg, luminal Af-Art diameter decreased in Dahl SR but not in Dahl SS (−3.1 ± 0.8 vs. 0.5 ± 0.8 μm, P < 0.01). The 20-HETE antagonist 20-HEDE (10−6 M) blocked the myogenic response in Dahl SR but had no effect in Dahl SS. Addition of a subconstrictor concentration of 20-HETE (but not a subconstrictor concentration of norepinephrine) restored the myogenic response in Dahl SS. We then perfused Af-Arts at 60 mmHg and tested the effects of the ATP analog α,β-methylene-ATP (10−6 M). Maximum ATP-induced constriction was attenuated in Dahl SS compared with Dahl SR (1.5 ± 0.5 vs. 7.4 ± 0.8 μm, P < 0.001). 20-HEDE attenuated ATP-induced Af-Art constriction in Dahl SR but not in Dahl SS, and consequently, ATP-induced constriction was no longer different between strains. In conclusion, Dahl SS have an impaired myogenic response and ATP-induced Af-Art constriction due to a decrease in Af-Art 20-HETE. The impaired myogenic responses may contribute to the nephrosclerosis that develops in Dahl SS.

  • abstract 520 na h exchanger participates in tubuloGlomerular feedback
    Hypertension, 2014
    Co-Authors: Hong Wang, Kristopher Kutskill, Martin A Dambrosio, Pablo Leung, Sumit R. Monu, Edward L. Peterson, Jeffrey L. Garvin, Yilin Ren, Oscar A Carretero
    Abstract:

    The afferent arteriole (Af-Art) accounts for most renal vasculature resistance, thus controlling Glomerular filtration and renal function. The nephron regulates Af-Art resistance via two mechanisms, the vasoconstrictor tubuloGlomerular feedback (TGF), initiated in the macula densa via Na/K/2Cl cotransporters (NKCC2), and the vasodilator connecting tubule Glomerular feedback (CTGF), initiated in the connecting tubule via the epithelial Na channels (ENaC). However, when TGF and CTGF are inhibited by furosemide and benzamil, a novel form of TGF is observed. We hypothesize that in addition to NKCC2, TGF can be initiated by Na/H exchangers (NHE). Furthermore, we hypothesize that when NKCC2 and NHE are blocked, CTGF causes Af-Art dilation. In vivo, using the nephron micropuncture technique, we performed two consecutive stop-flow Pressure (PSF) curves (an index of Glomerular Capillary Pressure) by increasing the perfusion of the nephron from 0 to 40 nL/min while adding drugs to the tubular perfusate. TGF was blocked by furosemide (vehicle -7.9±0.2 mmHg at 40 nL/min, furosemide -0.4±0.2; P We conclude that NHE in the nephron causes TGF when NKCC2 and ENaC are inhibited and that CTGF causes dilation of the Af-Art when TGF is completely blocked with NKCC2 and NHE inhibitors.

  • connecting tubule Glomerular feedback in hypertension
    Hypertension, 2013
    Co-Authors: Hong Wang, Martin A Dambrosio, Jeffrey L. Garvin, Oscar A Carretero
    Abstract:

    In Dahl salt-sensitive rats (Dahl SS), Glomerular Capillary Pressure increases in response to high salt intake and this is accompanied by significant Glomerular injury compared with spontaneously hypertensive rats with similar blood Pressure. Glomerular Capillary Pressure is controlled mainly by afferent arteriolar resistance, which is regulated by the vasoconstrictor tubule Glomerular feedback (TGF) and the vasodilator connecting TGF (CTGF). We hypothesized that Dahl SS have a decreased TGF response and enhanced TGF resetting compared with spontaneously hypertensive rats, and that these differences are attributable in part to an increase in CTGF. In vivo, using micropuncture we measured stop-flow Pressure (a surrogate of Glomerular Capillary Pressure). TGF was calculated as the maximal decrease in stop-flow Pressure caused by increasing nephron perfusion, TGF resetting as the attenuation in TGF induced by high salt diet, and CTGF as the difference in TGF response before and during CTGF inhibition with benzamil. Compared with spontaneously hypertensive rats, Dahl SS had (1) lower TGF responses in normal (6.6±0.1 versus 11.0±0.2 mm Hg; P P P P

  • abstract 552 aldosterone enhances connecting tubule Glomerular feedback ctgf
    Hypertension, 2013
    Co-Authors: Martin A Dambrosio, Pablo Leung, Jeffrey L. Garvin, Hong Wang, Oscar A Carretero
    Abstract:

    Increasing Na delivery to the connecting tubule (CNT) stimulates epithelial Na channels (ENaC) and dilates the afferent arteriole (Af-Art), a process we call connecting tubule Glomerular feedback (CTGF). We hypothesize that aldosterone (aldo) enhances CTGF via a nongenomic mechanism that stimulates CNT ENaC via GPR30 and/or mineralocorticoid receptors (MR). Rabbit Af-Arts and their adherent CNTs were microdissected and simultaneously perfused. Two consecutive CTGF curves were elicited by increasing luminal NaCl in the CNT. Addition of aldo 10 -8 M to the CNT potentiated CTGF, seen as a left-shift in the concentration of NaCl that elicited a half-maximal response (EC 50 ), see Figure. The MR blocker eplerenone (10 -5 M) prevented the enhancement of CTGF by aldo (control EC 50 = 32.4 ± 2.3 mM; aldo + eplerenone EC 50 = 35.4 ± 1.7 mM; n = 7). Neither the transcription inhibitor actinomycin D (5x10 -6 M) nor the translation inhibitor cycloheximide (10 -5 M) prevented the effect of aldo (control EC 50 = 33.0 ± 2.0 mM; aldo + actinomycin D EC 50 = 15.4 ± 1.5 mM; n = 6; P 50 = 33.2 ± 2.4 mM; aldo + cycloheximide EC 50 = 11.2 ± 1.3 mM; n = 6; P via a nongenomic effect possibly involving MR and/or GPR30 receptors. Enhanced CTGF induced by aldosterone may contribute to renal damage by causing increases in Af-Art dilation and Glomerular Capillary Pressure (Glomerular barotrauma). Figure. Control CTGF (○) seen as dilation of norepinephrine-preconstricted Af-Arts induced by increasing NaCl in the CNT. Aldo 10 -8 M (•) enhanced CTGF (n = 6; * P P P vs . control). Vertical dashed lines indicate EC 50 .

Sumit R. Monu - One of the best experts on this subject based on the ideXlab platform.

Christopher S. Wilcox - One of the best experts on this subject based on the ideXlab platform.

  • high salt diet induces outward remodelling of efferent arterioles in mice with reduced renal mass
    Acta Physiologica, 2017
    Co-Authors: Liang Zhao, Christopher S. Wilcox, Yufang Gao, Xiaoyun Cao, Danchen Gao, Suhan Zhou, Suping Zhang, Xiaoxia Cai, Feng Han, En Yin Lai
    Abstract:

    Aim The Glomerular filtration rate (GFR) falls progressively in chronic kidney disease (CKD) which is caused by a reduction in the number of functional nephrons. The dysfunctional nephron exhibits a lower Glomerular Capillary Pressure that is induced by an unbalance between afferent and efferent arteriole. Therefore, we tested the hypothesis that oxidative stress induced by CKD differentially impairs the structure or function of efferent versus afferent arterioles. Methods C57BL/6 mice received sham operations (sham) or 5/6 nephrectomy (RRM) and 3 months of normal or high salt diet or tempol. GFR was assessed from the plasma inulin clearance, arteriolar remodeling from media/lumen area ratio, myogenic responses from changes in luminal diameter with increases in perfusion Pressure and passive wall compliance from the wall stress/strain relationships. Results Mice with RRM fed a high salt (versus sham) had a lower GFR (553±25 versus 758±36μl/min/g kidney, p<0.01) and a larger efferent arteriolar diameter (9.6±0.8 versus 7.4±0.7μm, p<0.05) resulting in a lower media/lumen area ratio (1.4±0.1 versus 2.4±0.2, p<0.01). These alterations were corrected by tempol. The myogenic responses of efferent arterioles were about one-half that of afferent arterioles and were unaffected by RRM or salt. Passive wall compliance was reduced by high salt in both afferent and efferent arterioles. Conclusion A reduction in renal mass with a high salt diet induces oxidative stress that leads to an outward eutrophic remodeling in efferent arterioles and reduced wall compliance in both afferent and efferent arterioles. This may contribute to the lower GFR in this model of CKD. This article is protected by copyright. All rights reserved.

  • role of nitric oxide in tubuloGlomerular feedback effects of dietary salt
    Clinical and Experimental Pharmacology and Physiology, 1997
    Co-Authors: William J. Welch, Christopher S. Wilcox
    Abstract:

    SUMMARY 1. The tubuloGlomerular feedback (TGF) response operates primarily by vasoconstriction of the afferent arteriole and a fall in Glomerular Capillary Pressure (PGC) and single-nephron Glomerular nitration rate (SNGFR) during increased NaCl reabsorption in the macula densa (MD). Numerous studies have suggested that nitric oxide (NO) is synthesized by the MD and acts to suppress TGF. As a high-salt (HS) diet has been found to blunt TGF, we tested the effects of salt intake on NO-dependent changes in TGF. 2. In the first series of experiments, values of SNGFR were contrasted from samples of tubular fluid taken from the proximal tubule (PT; MD delivery interrupted) and the distal tubule (DT; MD delivery intact). Compared with HS rats, the difference between PT and DT values of SNGFR was increased in low-salt (LS) diet rats (4.3 ± 0.4 vs 10.3 ± 1.2 nL/min, respectively; P < 0.001). Intravenous infusion of iVG-monomethyl-L-arginine (L-NMMA), in pressor doses increased the difference between PT and DT values of SNGFR of HS rats (4.3 ± 0.4 vs 9.5 ± 1.2 nL/min before and during L-NMMA, respectively; P < 0.001) without significantly affecting values in LS rats (10.3 ± 1.2 vs 12.3 ± 1.4 nL/min before and during L-NMMA, respectively; NS). 3. A second series of experiments assessed TGF responses directly. Changes in stop-flow Pressure (PSF; an index of PGC) were measured in response to graded perfusion of the loop of Henle (LH) with artificial tubular fluid. Loop perfusion with 10-3 mol/1. L-NMMA did not affect the PSF responses of LS rats but did reduce (P < 0.01) the PSF of HS rats during perfusion at 20 nL/min (-1.5±0.4mmHg; P<0.01), 30nL/min (-1.8 ± O.5 mmHg; P < 0.01) and 40 nL/min (-2.2 ± 0.5 mmHg; P < 0.001). 4. We conclude that the TGF response is increased by suppression of NOS activity during HS but not LS intake.

  • immunocytochemical localization of distinct isoforms of nitric oxide synthase in the juxtaGlomerular apparatus of normal rat kidney
    Journal of The American Society of Nephrology, 1994
    Co-Authors: A Tojo, Christopher S. Wilcox, Steven S. Gross, Li Zhang, Craig C Tisher, H H Schmidt, Kirsten M Madsen
    Abstract:

    Nitric oxide (NO) is a messenger molecule that functions as a vasodilator and accounts for the biologic activity of endothelium-derived relaxing factor (EDRF). The enzyme responsible for NO production, NO synthase (NOS), exists in different isoforms. Some are expressed constitutively in various tissues, whereas others require induction by endotoxin and cytokines. There is evidence that NO plays an important role in the regulation of basal renal vascular resistance and in the tubuloGlomerular feedback response. Specific antibodies to a constitutive NOS isolated from rat brain (B-NOS) and an inducible NOS isolated from rat aortic smooth muscle (VSM-NOS) were used to establish the cellular and subcellular distribution of NOS in the kidney. Kidneys from normal rats were preserved and processed for light and electron microscopic immunohistochemical studies using both a preembedding and a postembedding horseradish peroxidase technique. By light microscopy, strong immunostaining for B-NOS was observed in the juxtaGlomerular apparatus, where it was located in cells of the macula densa. In contrast, immunostaining for VSM-NOS was specifically located in the terminal afferent arteriole and occasionally also in the initial efferent arteriole in the juxtaGlomerular apparatus. In addition, faint immunostaining was present in the entire distal tubule. There was no labeling of arcuate or interlobular arteries. The injection of lipopolysaccharide was associated with increased immunostaining for VSM-NOS in the afferent arteriole but had no effect on B-NOS staining. By electron microscopy, B-NOS immunostaining was present throughout the cytoplasm of the macula densa cells, where it appeared to be associated mainly with small vesicles. Immunostaining for VSM-NOS in the afferent arteriole exhibited a patchy distribution in some cells, whereas other cells were stained throughout the cytoplasm. These results indicate that two distinct isoforms of NOS are present in the juxtaGlomerular apparatus and support the hypothesis that NOS is involved in the regulation of tubuloGlomerular feedback and Glomerular Capillary Pressure.

  • Nitric oxide synthase in macula densa regulates Glomerular Capillary Pressure
    Proceedings of the National Academy of Sciences of the United States of America, 1992
    Co-Authors: Christopher S. Wilcox, William J. Welch, Ferid Murad, Steven S. Gross, Graham P. Taylor, Roberto Levi, Harald H.h.w. Schmidt
    Abstract:

    Abstract Tubular-fluid reabsorption by specialized cells of the nephron at the junction of the ascending limb of the loop of Henle and the distal convoluted tubule, termed the macula densa, releases compounds causing vasoconstriction of the adjacent afferent arteriole. Activation of this tubuloGlomerular feedback response reduces Glomerular Capillary Pressure of the nephron and, hence, the Glomerular filtration rate. The tubuloGlomerular feedback response functions in a negative-feedback mode to relate Glomerular Capillary Pressure to tubular-fluid delivery and reabsorption. This system has been implicated in renal autoregulation, renin release, and longterm body fluid and blood-Pressure homeostasis. Here we report that arginine-derived nitric oxide, generated in the macula densa, is an additional intercellular signaling molecule that is released during tubular-fluid reabsorption and counters the vasoconstriction of the afferent arteriole. Antibody to rat cerebellar constitutive nitric oxide synthase stained rat macula densa cells specifically. Microperfusion of the macula densa segment of single nephrons with N omega-methyl-L-arginine (an inhibitor of nitric oxide synthase) or with pyocyanin (a lipid-soluble inhibitor of endothelium-derived relaxation factor) showed that generation of nitric oxide can vasodilate the afferent arteriole and increase Glomerular Capillary Pressure; this effect was blocked by drugs that prevent tubular-fluid reabsorption. We conclude that nitric oxide synthase in macula densa cells is activated by tubular-fluid reabsorption and mediates a vasodilating component to the tubuloGlomerular feedback response. These findings imply a role for arginine-derived nitric oxide in body fluid-volume and blood-Pressure homeostasis, in addition to its established roles in modulation of vascular tone by the endothelium and in neurotransmission.

Martin A Dambrosio - One of the best experts on this subject based on the ideXlab platform.

  • mechanism of impaired afferent arteriole myogenic response in dahl salt sensitive rats role of 20 hete
    American Journal of Physiology-renal Physiology, 2014
    Co-Authors: Martin A Dambrosio, Edward L. Peterson, Jeffrey L. Garvin, Oscar A Carretero
    Abstract:

    The afferent arteriole (Af-Art) controls Glomerular Capillary Pressure, an important determinant of Glomerular injury. Af-Art myogenic response is mediated by ATP, and ATP signaling is in turn mediated by 20-HETE. Dahl salt-sensitive rats (Dahl SS) have decreased renal 20-HETE production. We hypothesized that Dahl SS have an impaired myogenic response and constrictor response to ATP, due to decreased 20-HETE. Af-Arts from Dahl SS or Dahl salt-resistant rats (Dahl SR) were microdissected and perfused. When myogenic response was induced by increasing Af-Art perfusion Pressure from 60 to 140 mmHg, luminal Af-Art diameter decreased in Dahl SR but not in Dahl SS (−3.1 ± 0.8 vs. 0.5 ± 0.8 μm, P < 0.01). The 20-HETE antagonist 20-HEDE (10−6 M) blocked the myogenic response in Dahl SR but had no effect in Dahl SS. Addition of a subconstrictor concentration of 20-HETE (but not a subconstrictor concentration of norepinephrine) restored the myogenic response in Dahl SS. We then perfused Af-Arts at 60 mmHg and tested the effects of the ATP analog α,β-methylene-ATP (10−6 M). Maximum ATP-induced constriction was attenuated in Dahl SS compared with Dahl SR (1.5 ± 0.5 vs. 7.4 ± 0.8 μm, P < 0.001). 20-HEDE attenuated ATP-induced Af-Art constriction in Dahl SR but not in Dahl SS, and consequently, ATP-induced constriction was no longer different between strains. In conclusion, Dahl SS have an impaired myogenic response and ATP-induced Af-Art constriction due to a decrease in Af-Art 20-HETE. The impaired myogenic responses may contribute to the nephrosclerosis that develops in Dahl SS.

  • abstract 520 na h exchanger participates in tubuloGlomerular feedback
    Hypertension, 2014
    Co-Authors: Hong Wang, Kristopher Kutskill, Martin A Dambrosio, Pablo Leung, Sumit R. Monu, Edward L. Peterson, Jeffrey L. Garvin, Yilin Ren, Oscar A Carretero
    Abstract:

    The afferent arteriole (Af-Art) accounts for most renal vasculature resistance, thus controlling Glomerular filtration and renal function. The nephron regulates Af-Art resistance via two mechanisms, the vasoconstrictor tubuloGlomerular feedback (TGF), initiated in the macula densa via Na/K/2Cl cotransporters (NKCC2), and the vasodilator connecting tubule Glomerular feedback (CTGF), initiated in the connecting tubule via the epithelial Na channels (ENaC). However, when TGF and CTGF are inhibited by furosemide and benzamil, a novel form of TGF is observed. We hypothesize that in addition to NKCC2, TGF can be initiated by Na/H exchangers (NHE). Furthermore, we hypothesize that when NKCC2 and NHE are blocked, CTGF causes Af-Art dilation. In vivo, using the nephron micropuncture technique, we performed two consecutive stop-flow Pressure (PSF) curves (an index of Glomerular Capillary Pressure) by increasing the perfusion of the nephron from 0 to 40 nL/min while adding drugs to the tubular perfusate. TGF was blocked by furosemide (vehicle -7.9±0.2 mmHg at 40 nL/min, furosemide -0.4±0.2; P We conclude that NHE in the nephron causes TGF when NKCC2 and ENaC are inhibited and that CTGF causes dilation of the Af-Art when TGF is completely blocked with NKCC2 and NHE inhibitors.

  • connecting tubule Glomerular feedback in hypertension
    Hypertension, 2013
    Co-Authors: Hong Wang, Martin A Dambrosio, Jeffrey L. Garvin, Oscar A Carretero
    Abstract:

    In Dahl salt-sensitive rats (Dahl SS), Glomerular Capillary Pressure increases in response to high salt intake and this is accompanied by significant Glomerular injury compared with spontaneously hypertensive rats with similar blood Pressure. Glomerular Capillary Pressure is controlled mainly by afferent arteriolar resistance, which is regulated by the vasoconstrictor tubule Glomerular feedback (TGF) and the vasodilator connecting TGF (CTGF). We hypothesized that Dahl SS have a decreased TGF response and enhanced TGF resetting compared with spontaneously hypertensive rats, and that these differences are attributable in part to an increase in CTGF. In vivo, using micropuncture we measured stop-flow Pressure (a surrogate of Glomerular Capillary Pressure). TGF was calculated as the maximal decrease in stop-flow Pressure caused by increasing nephron perfusion, TGF resetting as the attenuation in TGF induced by high salt diet, and CTGF as the difference in TGF response before and during CTGF inhibition with benzamil. Compared with spontaneously hypertensive rats, Dahl SS had (1) lower TGF responses in normal (6.6±0.1 versus 11.0±0.2 mm Hg; P P P P

  • abstract 552 aldosterone enhances connecting tubule Glomerular feedback ctgf
    Hypertension, 2013
    Co-Authors: Martin A Dambrosio, Pablo Leung, Jeffrey L. Garvin, Hong Wang, Oscar A Carretero
    Abstract:

    Increasing Na delivery to the connecting tubule (CNT) stimulates epithelial Na channels (ENaC) and dilates the afferent arteriole (Af-Art), a process we call connecting tubule Glomerular feedback (CTGF). We hypothesize that aldosterone (aldo) enhances CTGF via a nongenomic mechanism that stimulates CNT ENaC via GPR30 and/or mineralocorticoid receptors (MR). Rabbit Af-Arts and their adherent CNTs were microdissected and simultaneously perfused. Two consecutive CTGF curves were elicited by increasing luminal NaCl in the CNT. Addition of aldo 10 -8 M to the CNT potentiated CTGF, seen as a left-shift in the concentration of NaCl that elicited a half-maximal response (EC 50 ), see Figure. The MR blocker eplerenone (10 -5 M) prevented the enhancement of CTGF by aldo (control EC 50 = 32.4 ± 2.3 mM; aldo + eplerenone EC 50 = 35.4 ± 1.7 mM; n = 7). Neither the transcription inhibitor actinomycin D (5x10 -6 M) nor the translation inhibitor cycloheximide (10 -5 M) prevented the effect of aldo (control EC 50 = 33.0 ± 2.0 mM; aldo + actinomycin D EC 50 = 15.4 ± 1.5 mM; n = 6; P 50 = 33.2 ± 2.4 mM; aldo + cycloheximide EC 50 = 11.2 ± 1.3 mM; n = 6; P via a nongenomic effect possibly involving MR and/or GPR30 receptors. Enhanced CTGF induced by aldosterone may contribute to renal damage by causing increases in Af-Art dilation and Glomerular Capillary Pressure (Glomerular barotrauma). Figure. Control CTGF (○) seen as dilation of norepinephrine-preconstricted Af-Arts induced by increasing NaCl in the CNT. Aldo 10 -8 M (•) enhanced CTGF (n = 6; * P P P vs . control). Vertical dashed lines indicate EC 50 .

  • enhanced myogenic response in the afferent arteriole of spontaneously hypertensive rats
    American Journal of Physiology-heart and Circulatory Physiology, 2010
    Co-Authors: Martin A Dambrosio, Jeffrey L. Garvin, Patrick J Pagano, Oscar A Carretero
    Abstract:

    Spontaneously hypertensive rats (SHRs) have normal Glomerular Capillary Pressure even though renal perfusion Pressure is higher, suggesting that preGlomerular vessels exhibit abnormally high resist...