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Oscar A Carretero - One of the best experts on this subject based on the ideXlab platform.
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role of connecting tubule glomerular feedback in obesity related renal damage
American Journal of Physiology-renal Physiology, 2018Co-Authors: Sumit R. Monu, Mani Maheshwari, Edward L. Peterson, Oscar A CarreteroAbstract: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...
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crosstalk between the connecting tubule and the afferent Arteriole regulates renal microcirculation
Kidney International, 2007Co-Authors: Jeffrey L. Garvin, Oscar A CarreteroAbstract:The renal afferent Arterioles (Af-Arts) account for most of the renal vascular resistance, which is controlled similar to other Arterioles and by tubuloglomerular feedback (TGF). The latter signal is generated by sensing sodium chloride concentrations in the macula densa; this in turn results in a signal which acts through the extraglomerular mesangium leading to constriction of the Af-Art. In the outer renal cortex, the connecting tubule (CNT) returns to the glomerular hilus and contacts the Af-Art suggesting that crosstalk may exist here as well. To investigate this, we simultaneously perfused a microdissected Af-Art and adherent CNT. Increasing the sodium chloride concentration perfusing the CNT significantly dilated preconstricted Af-Arts. We called this crosstalk 'connecting tubule glomerular feedback' (CTGF) to differentiate it from TGF. We tested whether entry of Na þ and/or CIinto the CNT is required to induce CTGF by replacing Na þ with choline þ . Increasing choline chloride concentration did not dilate the Af-Art. To test whether epithelial Na channels (ENaCs) mediate CTGF, we blocked ENaC with amiloride and found that the dilatation induced by CTGF was completely blocked. Inhibiting sodium chloride cotransporters with hydrochlorothiazide failed to prevent Af-Art dilatation. Finally, we tested whether nitric oxide released by the CNT mediates CTGF by the addition of a non-selective nitric oxide synthase inhibitor to the CNT. This potentiated CTGF rather than blocking it. We suggest that crosstalk exists between CNTs and attached Af-Arts, which is initiated by sodium reabsorption through amiloride-sensitive channels and this can contribute to the regulation of renal blood flow and glomerular filtration. The renal afferent Arterioles (Af-Arts) account for most renal vascular resistance; they control glomerular filtration rate (GFR) and peritubular pressure, and thus renal function. In addition, Af-Art and Efferent Arteriole resistance control intraglomerular pressure, which is important not only for filtration pressure but also the development of glomerulo- sclerosis in hypertension and diabetes. Af-Art resistance is regulated by factors similar to other Arterioles, and in addition is controlled in part by tubuloglomerular feedback (TGF). TGF operates via the macula densa: when concentra- tions of sodium and chloride in the macula densa are increased, a signal is transmitted through the extraglomerular mesangium that constricts the Af-Art. 1 In humans and other mammals, there is a transitional region of the nephron between the distal convoluted tubule and the cortical collecting duct, called the connecting tubule (CNT). This segment of the nephron plays a significant role in the
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possible mechanism of Efferent Arteriole ef art tubuloglomerular feedback
Kidney International, 2007Co-Authors: Jeffrey L. Garvin, Oscar A CarreteroAbstract:Adenosine triphosphate (ATP) is liberated from macula densa cells in response to increased tubular NaCl delivery. However, it is not known whether ATP from the macula densa is broken down to adenosine, or whether this adenosine mediates Efferent Arteriole (Ef-Art) tubuloglomerular feedback (TGF). We hypothesized that increased macula densa Ca 2+ , release of ATP and degradation of ATP to adenosine are necessary for Ef-Art TGF. Rabbit Ef-Arts and adherent tubular segments (with the macula densa) were simultaneously microperfused in vitro while changing the NaCl concentration at the macula densa. The Ef-Art was perfused orthograde through the end of the afferent Arteriole (Af-Art). In Ef-Arts preconstricted with norepinephrine (NE), increasing NaCl concentration from 10 to 80mM at the macula densa dilated Ef-Arts from 7.5±0.7 to 11.1±0.3 μ m. Buffering increases in macula densa Ca 2+ with the cell-permeant Ca 2+ chelator BAPTA-AM diminished Ef-Art TGF from 3.1±0.3 to 0.1±0.2 μ m. Blocking adenosine formation by adding α - β -methyleneadenosine 5′-diphosphate (MADP) blocked Ef-Art TGF from 2.9±0.5 to 0.1±0.2 μ m. Increasing luminal NaCl at the macula densa from 10 to 45mM caused a moderate Ef-Art TGF response, 1.3±0.1 μ m. It was potentiated to 4.0±0.3 μ m by adding hexokinase, which enhances conversion of ATP into adenosine. Our data show that in vitro changes in macula densa Ca 2+ and ATP release are necessary for Ef-Art TGF. ATP is broken down to form adenosine, which mediates signal transmission of Ef-Art TGF.
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Efferent Arteriole tubuloglomerular feedback in the renal nephron
Kidney International, 2001Co-Authors: Jeffrey L. Garvin, Oscar A CarreteroAbstract:Efferent Arteriole tubuloglomerular feedback in the renal nephron. Background Afferent and Efferent Arteriole resistance exerts critical and opposite actions in the regulation of glomerular capillary pressure (P GC ) and glomerular filtration rate (GFR). Tubuloglomerular feedback (TGF) plays an important role in the regulation of afferent Arteriole resistance; however, the role of TGF in the regulation of Efferent Arteriole resistance is less well established. We hypothesized that TGF caused by increased NaCl in the tubular fluid stimulates the macula densa to initiate a cascade of events resulting in Efferent Arteriole vasodilation, mediated by adenosine via its A 2 receptor. Methods Rabbit Efferent Arterioles and adherent tubular segments with macula densa were simultaneously microperfused in vitro while changing NaCl concentration at the macula densa. To study whether autacoids produced by the glomerulus participate in the effect of TGF on Efferent Arterioles, they were perfused orthograde or retrograde. To eliminate the hemodynamic influence of the afferent Arteriole during orthograde perfusion, the perfusion pipette was advanced to the distal end of the afferent Arteriole, and the tip of the pressure pipette was placed beyond the afferent Arteriole; for retrograde perfusion, the Efferent Arteriole was perfused from its distal end. Results In Efferent Arterioles perfused orthograde and preconstricted with norepinephrine (NE), increasing NaCl concentration at the macula densa increased the diameter by 33%. In preconstricted Efferent Arterioles perfused retrograde, increasing NaCl at the macula densa increased the diameter by 33%. Efferent Arteriole vasodilation was completely blocked by a selective adenosine A 2 receptor antagonist (3,7-dimethyl-1-propargylxanthine) but not by an adenosine A 1 receptor antagonist (FK838). Conclusions Our data show that in vitro, preconstricted Efferent Arterioles dilate in response to increased macula densa NaCl, and this process is mediated by activation of adenosine A 2 receptors. Thus, TGF changes Efferent Arteriole resistance in the opposite direction from the afferent Arteriole, possibly amplifying TGF regulation of P GC and GFR. In vivo Efferent Arteriole TGF may only buffer the signals that cause Efferent Arteriole resistance to parallel changes in afferent Arteriole resistance. Effects of TGF on Efferent Arterioles perfused orthograde or retrograde were similar, suggesting that glomerular autacoids do not participate in this process.
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endothelium derived relaxing factor nitric oxide modulates angiotensin ii action in the isolated microperfused rabbit afferent but not Efferent Arteriole
Journal of Clinical Investigation, 1993Co-Authors: Shuji Arima, Luis A Juncos, Oscar A CarreteroAbstract:Abstract It has been reported that sensitivity to angiotensin II (Ang II) is higher in Efferent (Ef) than afferent (Af) Arterioles (Arts). We tested the hypothesis that this is due to arteriolar differences in the interaction between Ang II and endothelium-derived relaxing factor/nitric oxide (EDNO). Rabbit Af-Arts with glomerulus intact were microperfused in vitro at a constant pressure. Ef-Arts were perfused from the distal end of either the Af-Art (orthograde perfusion) or the Ef-Art (retrograde perfusion) to eliminate influences of the Af-Art or glomerulus, respectively. Ang II did not alter Af-Art luminal diameter until the concentration reached 10(-9) M, which decreased the diameter by 11 +/- 2.6% (n = 11; P < 0.002). In contrast, Ef-Arts became significantly constricted at concentrations as low as 10(-11) M with either perfusion. Surprisingly, the decrease in Ef-Art diameter at 10(-10), 10(-9), and 10(-8) M was significantly greater with retrograde perfusion (44 +/- 6.9%, 70 +/- 5.6%, and 74 +/- 4.1%, respectively; n = 5) than with orthograde perfusion (16 +/- 4.2%, 25 +/- 2.9%, and 35 +/- 3.5%; n = 9). ENDO synthesis inhibition with 10(-4) M nitro-L-arginine methyl ester (L-NAME) decreased the diameter to a greater extent in Af-Arts (22 +/- 3.0%; n = 11) compared to Ef-Arts with either orthograde (9.5 +/- 2.3%; n = 8) or retrograde perfusion (1.2 +/- 2.1%; n = 6). With L-NAME pretreatment, Af-Art constriction induced by 10(-10) M (14 +/- 4.0%, n = 9) and 10(-9) M Ang II (38 +/- 3.9%) was significantly greater compared to nontreated Af-Arts. In contrast, L-NAME pretreatment had no effect on Ang II-induced constriction in Ef-Arts with either perfusion. In conclusion, this study demonstrates higher sensitivity of Ef-Arts to Ang II, particularly with retrograde perfusion. Our results suggest that EDNO significantly modulates the vasoconstrictor action of Ang II in Af-Arts II but not Ef-Arts, contributing to the differential sensitivity to Ang II.
Rodger Loutzenhiser - One of the best experts on this subject based on the ideXlab platform.
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identification of voltage activated calcium currents in renal afferent and Efferent Arterioles of the rat
The FASEB Journal, 2012Co-Authors: Sergey V Smirnov, Kathy Loutzenhizer, Rodger LoutzenhiserAbstract:Based on indirect methods, it is suggested that both Land T-type Ca channels mediate signaling in the renal afferent Arteriole (AA) and that T-type Ca channels are involved in signaling in the Efferent Arteriole (EA). Our study was initiated to characterize Ca currents in these vessels, directly, using patch clamp. Native myocytes were isolated from individually isolated rat AA and EA and from tail arteries. Inward currents were measured in physiologic 1.5 mmol/L Ca and 10 mmol/L Ba using the whole-cell configuration. By exploiting known differences in activation and inactivation properties and sensitivities to nifedipine and kurtoxin, we could readily demonstrate the presence of both Land T-type Ca channels in myocytes from the rat tail artery. AA myocytes exhibited relatively large Ca current densities (–2.0±0.2 pA/pF), which increased 3.6 fold in Ba. These currents were blocked by nifedipine, but not by kurtoxin or mibefradil and did not exhibit the activation and inactivation characteristics of T-type Ca channels, compared to tail artery myocytes. EA myocytes did not exhibit a marked voltage-activated inward current in 1.5 mmol/L Ca. Thus, our findings support the physiologic role of Ltype Ca channels in the AA, but not EA, and do not support the premise that Ttype Ca channels are significantly present in either vessel. Supported by the Royal Society and the Alberta Heritage Foundation for Medical Research. Page 1 of 2 Identification of Voltage-Activated Calcium Currents in Renal Afferent and Efferent Arterioles of th...
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inward rectifier k currents and kir2 1 expression in renal afferent and Efferent Arterioles
Journal of The American Society of Nephrology, 2008Co-Authors: Lisa Chilton, Kathy Loutzenhiser, Gary J Kargacin, Ezequiel Morales, Jennifer Breaks, Rodger LoutzenhiserAbstract:The afferent and Efferent Arterioles regulate the inflow and outflow resistance of the glomerulus, acting in concert to control the glomerular capillary pressure and glomerular filtration rate. The myocytes of these two vessels are remarkably different, especially regarding electromechanical coupling. This study investigated the expression and function of inward rectifier K+ channels in these two vessels using perfused hydronephrotic rat kidneys and Arterioles and myocytes isolated from normal rat kidneys. In afferent Arterioles pre-constricted with angiotensin II, elevating [K+]0 from 5 to 15 mmol/L induced hyperpolarization (–27 ± 2 to –41 ± 3 mV) and vasodilation (6.6 ± 0.9 to 13.1 ± 0.6 µm). This manipulation also attenuated angiotensin II-induced Ca2+ signaling, an effect blocked by 100 µmol/L Ba2+. By contrast, elevating [K+]0 did not alter angiotensin II-induced Ca2+ signaling or vasoconstriction in Efferent Arterioles, even though a significant hyperpolarization was observed (from –30 ± 1 to –37 ± 3 mV, P = 0.003). Both vessels expressed mRNA for Kir2.1 and exhibited anti-Kir2.1 antibody labeling. Patch-clamp measurements revealed prominent inwardly rectifying and Ba2+-sensitive currents in afferent and Efferent arteriolar myocytes. Our findings indicate that both Arterioles express an inward rectifier K+ current, but that modulation of this current alters responsiveness of only the afferent Arteriole. The expression of Kir in the Efferent Arteriole, a resistance vessel whose tone is not affected by membrane potential, is intriguing and may suggest a novel function of this channel in the renal microcirculation.
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myosin heavy chain expression in renal afferent and Efferent Arterioles relationship to contractile kinetics and function
The FASEB Journal, 2003Co-Authors: Mitsuya Shiraishi, Michael P. Walsh, Xuemei Wang, Kathy Loutzenhiser, Gary J Kargacin, Rodger LoutzenhiserAbstract:The physiological role of smooth muscle myosin heavy chain (MHC) isoform diversity is poorly understood. The expression of MHC-B, which contains an insert at the ATP binding pocket, has been linked to enhanced contractile kinetics. We recently reported that the renal afferent Arteriole exhibits an unusually rapid myogenic response and that its kinetic features allow this vessel to modulate tone in response to alterations in systolic blood pressure. In the present study, we examined MHC expression patterns in renal afferent and Efferent Arterioles. These two vessels regulate glomerular inflow and outflow resistances and control the pressure within the intervening glomerular capillaries (PGC). Whereas the afferent Arteriole must respond rapidly to increases in blood pressure, the Efferent Arteriole plays a distinctly different role, maintaining a tonic elevation in outflow resistance to preserve function when renal perfusion is compromised. Using RT-PCR, Western analysis, and immunofluorescence imaging of intact isolated Arterioles, we found that the afferent Arteriole predominantly expresses the MHC-B isoform, whereas the Efferent Arteriole expresses only the slower-cycling MHC-A isoform. We examined the kinetics of angiotensin II- and norepinephrine-induced vasoconstriction and found that the afferent Arteriole responds approximately 3-fold faster than the Efferent Arteriole. Our findings thus point to the renal microcirculation as a unique and important example of smooth muscle adaptation in regard to MHC isoform expression and physiological function.
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angiotensin ii induced ca 2 influx in renal afferent and Efferent Arterioles differing roles of voltage gated and store operated ca 2 entry
Circulation Research, 2000Co-Authors: Kathy Loutzenhiser, Rodger LoutzenhiserAbstract:Angiotensin II (Ang II)-induced Ca(2+) signaling was studied in isolated rat renal Arterioles using fura-2. Ang II (10 nmol/L) caused a sustained elevation in [Ca(2+)](i), which was dependent on [Ca(2+)](o) in both vessel types. This response was blocked by nifedipine in only the afferent Arteriole. Using the Mn(2+) quench technique, we found that Ang II stimulates Ca(2+) influx in both vessels. Nifedipine blocked the Ang II-induced Ca(2+) influx in afferent Arterioles but not in Efferent Arterioles. In contrast to Ang II, KCl-induced depolarization stimulated Ca(2+) influx in only the afferent Arteriole. Cyclopiazonic acid (CPA, 30 micromol/L) was used to examine the presence of store-operated Ca(2+) entry in myocytes isolated from each Arteriole. In Efferent myocytes, CPA induced a sustained Ca(2+) increase that was dependent on [Ca(2+)](o) and insensitive to nifedipine. This mechanism was absent in afferent myocytes. SKF 96365 inhibited Ang II-induced Ca(2+) entry in Efferent Arterioles and CPA-induced Ca(2+) entry in Efferent myocytes over identical concentrations. Our findings thus indicate that Ang II activates differing Ca(2+) influx mechanisms in pre- and postglomerular Arterioles. In the afferent Arteriole, Ang II activates dihydropyridine-sensitive L-type Ca(2+) channels, presumably by membrane depolarization. In the Efferent Arteriole, Ang II appears to stimulate Ca(2+) entry via store-operated Ca(2+) influx.
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biphasic actions of prostaglandin e 2 on the renal afferent Arteriole role of ep 3 and ep 4 receptors
Circulation Research, 2000Co-Authors: Lilong Tang, Kathy Loutzenhiser, Rodger LoutzenhiserAbstract:Abstract —Prostaglandin (PG) E2 is an important modulator of the actions of angiotensin (Ang) II. In the present study, we investigated the renal microvascular actions of PGE2 and the EP receptor subtypes involved. Ibuprofen potentiated Ang II–induced vasoconstriction in in vitro perfused normal rat kidneys and augmented afferent arteriolar, but not Efferent arteriolar, responses in the hydronephrotic rat kidney model. This preglomerular effect of endogenous prostanoids was mimicked by exogenous PGE2, which reversed Ang II–induced afferent arteriolar vasoconstriction at concentrations of 0.1 to 10 nmol/L without affecting the Efferent Arteriole. The PGE2-induced vasodilation was potentiated by the phosphodiesterase inhibitor Ro 20-1724 and was mimicked by 11-deoxy-PGE1 (0.01 to 1 nmol/L). Butaprost, which acts preferentially at EP2 receptors, was relatively ineffective. Whereas 0.1 to 10 nmol/L PGE2 elicited vasodilation, higher concentrations (1 to 10 μmol/L) restored Ang II–induced afferent arteriolar vasoconstriction. This response was blocked by pertussis toxin (200 μg/mL) and was mimicked by the EP1/EP3 agonist sulprostone (1 to 300 nmol/L). Reverse transcription–polymerase chain reaction of individually isolated afferent Arterioles revealed the presence of message for EP4 and all 3 EP3 splice variants (α, β, and γ) but not EP1 or EP2. Our findings thus indicate that PGE2 elicits both vasodilatory and vasoconstrictor actions on the afferent Arteriole. The vasodilation is mediated by EP4 receptors coupled to cAMP, presumably via Gαs. The vasoconstriction is mediated by an EP3 receptor coupled to Gαi and appears to reflect a functional antagonism of the EP4-induced vasodilation.
Jeffrey L. Garvin - One of the best experts on this subject based on the ideXlab platform.
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crosstalk between the connecting tubule and the afferent Arteriole regulates renal microcirculation
Kidney International, 2007Co-Authors: Jeffrey L. Garvin, Oscar A CarreteroAbstract:The renal afferent Arterioles (Af-Arts) account for most of the renal vascular resistance, which is controlled similar to other Arterioles and by tubuloglomerular feedback (TGF). The latter signal is generated by sensing sodium chloride concentrations in the macula densa; this in turn results in a signal which acts through the extraglomerular mesangium leading to constriction of the Af-Art. In the outer renal cortex, the connecting tubule (CNT) returns to the glomerular hilus and contacts the Af-Art suggesting that crosstalk may exist here as well. To investigate this, we simultaneously perfused a microdissected Af-Art and adherent CNT. Increasing the sodium chloride concentration perfusing the CNT significantly dilated preconstricted Af-Arts. We called this crosstalk 'connecting tubule glomerular feedback' (CTGF) to differentiate it from TGF. We tested whether entry of Na þ and/or CIinto the CNT is required to induce CTGF by replacing Na þ with choline þ . Increasing choline chloride concentration did not dilate the Af-Art. To test whether epithelial Na channels (ENaCs) mediate CTGF, we blocked ENaC with amiloride and found that the dilatation induced by CTGF was completely blocked. Inhibiting sodium chloride cotransporters with hydrochlorothiazide failed to prevent Af-Art dilatation. Finally, we tested whether nitric oxide released by the CNT mediates CTGF by the addition of a non-selective nitric oxide synthase inhibitor to the CNT. This potentiated CTGF rather than blocking it. We suggest that crosstalk exists between CNTs and attached Af-Arts, which is initiated by sodium reabsorption through amiloride-sensitive channels and this can contribute to the regulation of renal blood flow and glomerular filtration. The renal afferent Arterioles (Af-Arts) account for most renal vascular resistance; they control glomerular filtration rate (GFR) and peritubular pressure, and thus renal function. In addition, Af-Art and Efferent Arteriole resistance control intraglomerular pressure, which is important not only for filtration pressure but also the development of glomerulo- sclerosis in hypertension and diabetes. Af-Art resistance is regulated by factors similar to other Arterioles, and in addition is controlled in part by tubuloglomerular feedback (TGF). TGF operates via the macula densa: when concentra- tions of sodium and chloride in the macula densa are increased, a signal is transmitted through the extraglomerular mesangium that constricts the Af-Art. 1 In humans and other mammals, there is a transitional region of the nephron between the distal convoluted tubule and the cortical collecting duct, called the connecting tubule (CNT). This segment of the nephron plays a significant role in the
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possible mechanism of Efferent Arteriole ef art tubuloglomerular feedback
Kidney International, 2007Co-Authors: Jeffrey L. Garvin, Oscar A CarreteroAbstract:Adenosine triphosphate (ATP) is liberated from macula densa cells in response to increased tubular NaCl delivery. However, it is not known whether ATP from the macula densa is broken down to adenosine, or whether this adenosine mediates Efferent Arteriole (Ef-Art) tubuloglomerular feedback (TGF). We hypothesized that increased macula densa Ca 2+ , release of ATP and degradation of ATP to adenosine are necessary for Ef-Art TGF. Rabbit Ef-Arts and adherent tubular segments (with the macula densa) were simultaneously microperfused in vitro while changing the NaCl concentration at the macula densa. The Ef-Art was perfused orthograde through the end of the afferent Arteriole (Af-Art). In Ef-Arts preconstricted with norepinephrine (NE), increasing NaCl concentration from 10 to 80mM at the macula densa dilated Ef-Arts from 7.5±0.7 to 11.1±0.3 μ m. Buffering increases in macula densa Ca 2+ with the cell-permeant Ca 2+ chelator BAPTA-AM diminished Ef-Art TGF from 3.1±0.3 to 0.1±0.2 μ m. Blocking adenosine formation by adding α - β -methyleneadenosine 5′-diphosphate (MADP) blocked Ef-Art TGF from 2.9±0.5 to 0.1±0.2 μ m. Increasing luminal NaCl at the macula densa from 10 to 45mM caused a moderate Ef-Art TGF response, 1.3±0.1 μ m. It was potentiated to 4.0±0.3 μ m by adding hexokinase, which enhances conversion of ATP into adenosine. Our data show that in vitro changes in macula densa Ca 2+ and ATP release are necessary for Ef-Art TGF. ATP is broken down to form adenosine, which mediates signal transmission of Ef-Art TGF.
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Efferent Arteriole tubuloglomerular feedback in the renal nephron
Kidney International, 2001Co-Authors: Jeffrey L. Garvin, Oscar A CarreteroAbstract:Efferent Arteriole tubuloglomerular feedback in the renal nephron. Background Afferent and Efferent Arteriole resistance exerts critical and opposite actions in the regulation of glomerular capillary pressure (P GC ) and glomerular filtration rate (GFR). Tubuloglomerular feedback (TGF) plays an important role in the regulation of afferent Arteriole resistance; however, the role of TGF in the regulation of Efferent Arteriole resistance is less well established. We hypothesized that TGF caused by increased NaCl in the tubular fluid stimulates the macula densa to initiate a cascade of events resulting in Efferent Arteriole vasodilation, mediated by adenosine via its A 2 receptor. Methods Rabbit Efferent Arterioles and adherent tubular segments with macula densa were simultaneously microperfused in vitro while changing NaCl concentration at the macula densa. To study whether autacoids produced by the glomerulus participate in the effect of TGF on Efferent Arterioles, they were perfused orthograde or retrograde. To eliminate the hemodynamic influence of the afferent Arteriole during orthograde perfusion, the perfusion pipette was advanced to the distal end of the afferent Arteriole, and the tip of the pressure pipette was placed beyond the afferent Arteriole; for retrograde perfusion, the Efferent Arteriole was perfused from its distal end. Results In Efferent Arterioles perfused orthograde and preconstricted with norepinephrine (NE), increasing NaCl concentration at the macula densa increased the diameter by 33%. In preconstricted Efferent Arterioles perfused retrograde, increasing NaCl at the macula densa increased the diameter by 33%. Efferent Arteriole vasodilation was completely blocked by a selective adenosine A 2 receptor antagonist (3,7-dimethyl-1-propargylxanthine) but not by an adenosine A 1 receptor antagonist (FK838). Conclusions Our data show that in vitro, preconstricted Efferent Arterioles dilate in response to increased macula densa NaCl, and this process is mediated by activation of adenosine A 2 receptors. Thus, TGF changes Efferent Arteriole resistance in the opposite direction from the afferent Arteriole, possibly amplifying TGF regulation of P GC and GFR. In vivo Efferent Arteriole TGF may only buffer the signals that cause Efferent Arteriole resistance to parallel changes in afferent Arteriole resistance. Effects of TGF on Efferent Arterioles perfused orthograde or retrograde were similar, suggesting that glomerular autacoids do not participate in this process.
Kathy Loutzenhiser - One of the best experts on this subject based on the ideXlab platform.
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inward rectifier k currents and kir2 1 expression in renal afferent and Efferent Arterioles
Journal of The American Society of Nephrology, 2008Co-Authors: Lisa Chilton, Kathy Loutzenhiser, Gary J Kargacin, Ezequiel Morales, Jennifer Breaks, Rodger LoutzenhiserAbstract:The afferent and Efferent Arterioles regulate the inflow and outflow resistance of the glomerulus, acting in concert to control the glomerular capillary pressure and glomerular filtration rate. The myocytes of these two vessels are remarkably different, especially regarding electromechanical coupling. This study investigated the expression and function of inward rectifier K+ channels in these two vessels using perfused hydronephrotic rat kidneys and Arterioles and myocytes isolated from normal rat kidneys. In afferent Arterioles pre-constricted with angiotensin II, elevating [K+]0 from 5 to 15 mmol/L induced hyperpolarization (–27 ± 2 to –41 ± 3 mV) and vasodilation (6.6 ± 0.9 to 13.1 ± 0.6 µm). This manipulation also attenuated angiotensin II-induced Ca2+ signaling, an effect blocked by 100 µmol/L Ba2+. By contrast, elevating [K+]0 did not alter angiotensin II-induced Ca2+ signaling or vasoconstriction in Efferent Arterioles, even though a significant hyperpolarization was observed (from –30 ± 1 to –37 ± 3 mV, P = 0.003). Both vessels expressed mRNA for Kir2.1 and exhibited anti-Kir2.1 antibody labeling. Patch-clamp measurements revealed prominent inwardly rectifying and Ba2+-sensitive currents in afferent and Efferent arteriolar myocytes. Our findings indicate that both Arterioles express an inward rectifier K+ current, but that modulation of this current alters responsiveness of only the afferent Arteriole. The expression of Kir in the Efferent Arteriole, a resistance vessel whose tone is not affected by membrane potential, is intriguing and may suggest a novel function of this channel in the renal microcirculation.
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myosin heavy chain expression in renal afferent and Efferent Arterioles relationship to contractile kinetics and function
The FASEB Journal, 2003Co-Authors: Mitsuya Shiraishi, Michael P. Walsh, Xuemei Wang, Kathy Loutzenhiser, Gary J Kargacin, Rodger LoutzenhiserAbstract:The physiological role of smooth muscle myosin heavy chain (MHC) isoform diversity is poorly understood. The expression of MHC-B, which contains an insert at the ATP binding pocket, has been linked to enhanced contractile kinetics. We recently reported that the renal afferent Arteriole exhibits an unusually rapid myogenic response and that its kinetic features allow this vessel to modulate tone in response to alterations in systolic blood pressure. In the present study, we examined MHC expression patterns in renal afferent and Efferent Arterioles. These two vessels regulate glomerular inflow and outflow resistances and control the pressure within the intervening glomerular capillaries (PGC). Whereas the afferent Arteriole must respond rapidly to increases in blood pressure, the Efferent Arteriole plays a distinctly different role, maintaining a tonic elevation in outflow resistance to preserve function when renal perfusion is compromised. Using RT-PCR, Western analysis, and immunofluorescence imaging of intact isolated Arterioles, we found that the afferent Arteriole predominantly expresses the MHC-B isoform, whereas the Efferent Arteriole expresses only the slower-cycling MHC-A isoform. We examined the kinetics of angiotensin II- and norepinephrine-induced vasoconstriction and found that the afferent Arteriole responds approximately 3-fold faster than the Efferent Arteriole. Our findings thus point to the renal microcirculation as a unique and important example of smooth muscle adaptation in regard to MHC isoform expression and physiological function.
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angiotensin ii induced ca 2 influx in renal afferent and Efferent Arterioles differing roles of voltage gated and store operated ca 2 entry
Circulation Research, 2000Co-Authors: Kathy Loutzenhiser, Rodger LoutzenhiserAbstract:Angiotensin II (Ang II)-induced Ca(2+) signaling was studied in isolated rat renal Arterioles using fura-2. Ang II (10 nmol/L) caused a sustained elevation in [Ca(2+)](i), which was dependent on [Ca(2+)](o) in both vessel types. This response was blocked by nifedipine in only the afferent Arteriole. Using the Mn(2+) quench technique, we found that Ang II stimulates Ca(2+) influx in both vessels. Nifedipine blocked the Ang II-induced Ca(2+) influx in afferent Arterioles but not in Efferent Arterioles. In contrast to Ang II, KCl-induced depolarization stimulated Ca(2+) influx in only the afferent Arteriole. Cyclopiazonic acid (CPA, 30 micromol/L) was used to examine the presence of store-operated Ca(2+) entry in myocytes isolated from each Arteriole. In Efferent myocytes, CPA induced a sustained Ca(2+) increase that was dependent on [Ca(2+)](o) and insensitive to nifedipine. This mechanism was absent in afferent myocytes. SKF 96365 inhibited Ang II-induced Ca(2+) entry in Efferent Arterioles and CPA-induced Ca(2+) entry in Efferent myocytes over identical concentrations. Our findings thus indicate that Ang II activates differing Ca(2+) influx mechanisms in pre- and postglomerular Arterioles. In the afferent Arteriole, Ang II activates dihydropyridine-sensitive L-type Ca(2+) channels, presumably by membrane depolarization. In the Efferent Arteriole, Ang II appears to stimulate Ca(2+) entry via store-operated Ca(2+) influx.
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biphasic actions of prostaglandin e 2 on the renal afferent Arteriole role of ep 3 and ep 4 receptors
Circulation Research, 2000Co-Authors: Lilong Tang, Kathy Loutzenhiser, Rodger LoutzenhiserAbstract:Abstract —Prostaglandin (PG) E2 is an important modulator of the actions of angiotensin (Ang) II. In the present study, we investigated the renal microvascular actions of PGE2 and the EP receptor subtypes involved. Ibuprofen potentiated Ang II–induced vasoconstriction in in vitro perfused normal rat kidneys and augmented afferent arteriolar, but not Efferent arteriolar, responses in the hydronephrotic rat kidney model. This preglomerular effect of endogenous prostanoids was mimicked by exogenous PGE2, which reversed Ang II–induced afferent arteriolar vasoconstriction at concentrations of 0.1 to 10 nmol/L without affecting the Efferent Arteriole. The PGE2-induced vasodilation was potentiated by the phosphodiesterase inhibitor Ro 20-1724 and was mimicked by 11-deoxy-PGE1 (0.01 to 1 nmol/L). Butaprost, which acts preferentially at EP2 receptors, was relatively ineffective. Whereas 0.1 to 10 nmol/L PGE2 elicited vasodilation, higher concentrations (1 to 10 μmol/L) restored Ang II–induced afferent arteriolar vasoconstriction. This response was blocked by pertussis toxin (200 μg/mL) and was mimicked by the EP1/EP3 agonist sulprostone (1 to 300 nmol/L). Reverse transcription–polymerase chain reaction of individually isolated afferent Arterioles revealed the presence of message for EP4 and all 3 EP3 splice variants (α, β, and γ) but not EP1 or EP2. Our findings thus indicate that PGE2 elicits both vasodilatory and vasoconstrictor actions on the afferent Arteriole. The vasodilation is mediated by EP4 receptors coupled to cAMP, presumably via Gαs. The vasoconstriction is mediated by an EP3 receptor coupled to Gαi and appears to reflect a functional antagonism of the EP4-induced vasodilation.
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bradykinin causes selective Efferent arteriolar dilation during angiotensin i converting enzyme inhibition
Kidney International, 1993Co-Authors: Agnes B Fogo, Iekuni Ichikawa, Samuel E Hellings, Teresa BillsAbstract:Bradykinin causes selective Efferent arteriolar dilation during angiotensin I converting enzyme inhibition. We studied the effects of interruption of the renin-angiotensin system (RAS) in rats that were volume depleted by water deprivation for 48 hours (AWD) with/without furosemide (AWD + F), a condition known to activate RAS. Following baseline micropuncture, AWD rats (N = 6) were treated with a specific angiotensin II type 1 receptor antagonist (AURA; 4 mg/kg body wt bolus i.v. and then continuous infusion) and glomerular hemodynamics compared to those obtained during angiotensin I converting enzyme inhibitor treatment (ACEI; 24 mg/kg bolus i.v. and then continuous infusion). Systemic blood pressure decreased equally following AIIRA and ACEI. Single nephron glomerular filtration rate (SNGFR) increased from baseline following AIIRA (24 nl/min vs. 30, P E ) reduced glomerular capillary pressure (P Gc 67 mm Hg vs. 60, P E together with decrease in afferent arteriolar resistance (R A ), enhanced glomerular plasma flow rate (Q A ; 80 nl/min vs. 111). Antagonizing angiotensin II receptor increased Q A which, together with the tendency to increase glomerular capillary ultrafiltration coefficient, K f , served to improve glomerular filtration. By contrast, although inhibition of the angiotensin I converting enzyme caused greater vasodilatation, no increase in SNGFR occurred. The lack of response in filtration after ACEI was due to a further fall in P GC to 52 mm Hg (P E . Since ACEI but not AIIRA potentiates bradykinin activity we examined effects of a specific bradykinin antagonist (Hoe). In a separate group of AWD+F rats (N = 6), ACEI again caused significant renal vasodilatation without affecting filtration rate. The ACEI-induced decrease in resistances was substantially antagonized by inhibition of bradykinin activity. Thus, Hoe significantly increased R E , effectively raising P GC by 9 mm Hg (P GC is crucial in maintaining GFR, activation of bradykinin by ACEI can compromise GFR secondary to bradykinin's selective vasodilatory action on the Efferent Arteriole.
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bradykinin causes selective Efferent arteriolar dilation during angiotensin i converting enzyme inhibition
Kidney International, 1993Co-Authors: Valentina Kon, Agnes B Fogo, Iekuni Ichikawa, Samuel E Hellings, Teresa BillsAbstract:Bradykinin causes selective Efferent arteriolar dilation during angiotensin I converting enzyme inhibition. We studied the effects of interruption of the renin-angiotensin system (RAS) in rats that were volume depleted by water deprivation for 48 hours (AWD) with/without furosemide (AWD + F), a condition known to activate RAS. Following baseline micropuncture, AWD rats (N = 6) were treated with a specific angiotensin II type 1 receptor antagonist (AURA; 4 mg/kg body wt bolus i.v. and then continuous infusion) and glomerular hemodynamics compared to those obtained during angiotensin I converting enzyme inhibitor treatment (ACEI; 24 mg/kg bolus i.v. and then continuous infusion). Systemic blood pressure decreased equally following AIIRA and ACEI. Single nephron glomerular filtration rate (SNGFR) increased from baseline following AIIRA (24 nl/min vs. 30, P E ) reduced glomerular capillary pressure (P Gc 67 mm Hg vs. 60, P E together with decrease in afferent arteriolar resistance (R A ), enhanced glomerular plasma flow rate (Q A ; 80 nl/min vs. 111). Antagonizing angiotensin II receptor increased Q A which, together with the tendency to increase glomerular capillary ultrafiltration coefficient, K f , served to improve glomerular filtration. By contrast, although inhibition of the angiotensin I converting enzyme caused greater vasodilatation, no increase in SNGFR occurred. The lack of response in filtration after ACEI was due to a further fall in P GC to 52 mm Hg (P E . Since ACEI but not AIIRA potentiates bradykinin activity we examined effects of a specific bradykinin antagonist (Hoe). In a separate group of AWD+F rats (N = 6), ACEI again caused significant renal vasodilatation without affecting filtration rate. The ACEI-induced decrease in resistances was substantially antagonized by inhibition of bradykinin activity. Thus, Hoe significantly increased R E , effectively raising P GC by 9 mm Hg (P GC is crucial in maintaining GFR, activation of bradykinin by ACEI can compromise GFR secondary to bradykinin's selective vasodilatory action on the Efferent Arteriole.
