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Thomas C. Lauenstein - One of the best experts on this subject based on the ideXlab platform.
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new look at Renal Vasculature 7 tesla nonenhanced t1 weighted flash imaging
Journal of Magnetic Resonance Imaging, 2012Co-Authors: Lale Umutlu, Stefan Maderwald, Oliver Kraff, Sonja Kinner, Lc Schaefer, Karsten H. Wrede, Gerald Antoch, Michael Forsting, Mark E. Ladd, Thomas C. LauensteinAbstract:Purpose: To investigate the feasibility of 7 Tesla (T) nonenhanced high field MR imaging of the Renal Vasculature and to evaluate the diagnostic potential of various nonenhanced T1-weighted (T1w) sequences. Materials and Methods: Twelve healthy volunteers were examined on a 7T whole-body MR system (Magnetom 7T, Siemens Healthcare Sector) using a custom-built eight-channel radiofrequency (RF) transmit/receive body coil. Subsequent to RF shimming, the following sequences were acquired (i) fat-saturated two-dimensional (2D) FLASH, (ii) fat-saturated 3D FLASH, and a (iii) fat-saturated 2D time-of-flight MR angiography (TOF MRA). SNR and CNR were measured in the aorta and both Renal arteries. Qualitative analysis was performed with regard to vessel delineation (5-point scale: 5 = excellent to 1 = nondiagnostic) and presence of artifacts (5-point scale: 5 = no artifact present to 1 = strong impairment). Results: The inherently high signal intensity of the Renal arterial Vasculature in T1w imaging enabled moderate to excellent vessel delineation in all sequences. Qualitative (mean, 4.7) and quantitative analysis (SNRmean: 53.9; CNRmean: 28.0) demonstrated the superiority of TOF MRA, whereas 2D FLASH imaging provided poorest vessel delineation and was most strongly impaired by artifacts (overall impairment 3.7). The 3D FLASH MRI demonstrated its potential for fast high quality imaging of the nonenhanced arterial Vasculature, providing homogeneous hyperintense vessel signal. Conclusion: Nonenhanced T1w imaging in general and, TOF MRA in particular, appear to be promising techniques for good quality nonenhanced Renal artery assessment at 7 Tesla. J. Magn. Reson. Imaging 2012;36:714–721. © 2012 Wiley Periodicals, Inc.
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New look at Renal Vasculature: 7 tesla nonenhanced T1‐weighted FLASH imaging
Journal of magnetic resonance imaging : JMRI, 2012Co-Authors: Lale Umutlu, Stefan Maderwald, Oliver Kraff, Sonja Kinner, Lc Schaefer, Karsten H. Wrede, Gerald Antoch, Michael Forsting, Mark E. Ladd, Thomas C. LauensteinAbstract:Purpose: To investigate the feasibility of 7 Tesla (T) nonenhanced high field MR imaging of the Renal Vasculature and to evaluate the diagnostic potential of various nonenhanced T1-weighted (T1w) sequences. Materials and Methods: Twelve healthy volunteers were examined on a 7T whole-body MR system (Magnetom 7T, Siemens Healthcare Sector) using a custom-built eight-channel radiofrequency (RF) transmit/receive body coil. Subsequent to RF shimming, the following sequences were acquired (i) fat-saturated two-dimensional (2D) FLASH, (ii) fat-saturated 3D FLASH, and a (iii) fat-saturated 2D time-of-flight MR angiography (TOF MRA). SNR and CNR were measured in the aorta and both Renal arteries. Qualitative analysis was performed with regard to vessel delineation (5-point scale: 5 = excellent to 1 = nondiagnostic) and presence of artifacts (5-point scale: 5 = no artifact present to 1 = strong impairment). Results: The inherently high signal intensity of the Renal arterial Vasculature in T1w imaging enabled moderate to excellent vessel delineation in all sequences. Qualitative (mean, 4.7) and quantitative analysis (SNRmean: 53.9; CNRmean: 28.0) demonstrated the superiority of TOF MRA, whereas 2D FLASH imaging provided poorest vessel delineation and was most strongly impaired by artifacts (overall impairment 3.7). The 3D FLASH MRI demonstrated its potential for fast high quality imaging of the nonenhanced arterial Vasculature, providing homogeneous hyperintense vessel signal. Conclusion: Nonenhanced T1w imaging in general and, TOF MRA in particular, appear to be promising techniques for good quality nonenhanced Renal artery assessment at 7 Tesla. J. Magn. Reson. Imaging 2012;36:714–721. © 2012 Wiley Periodicals, Inc.
Pernille B. Lærkegaard Hansen - One of the best experts on this subject based on the ideXlab platform.
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New Role of P/Q-type Voltage-gated Calcium Channels: From Transmitter Release to Contraction of Renal Vasculature.
Journal of cardiovascular pharmacology, 2015Co-Authors: Pernille B. Lærkegaard HansenAbstract:Voltage-gated calcium channels are important for the depolarization-evoked contraction of vascular smooth muscle cells (SMCs), with L-type channels being the classical channel involved in this mechanism. However, it has been demonstrated that the CaV2.1 subunit, which encodes a neuronal isoform of the voltage-gated calcium channels (P/Q-type), is also expressed and contributes functionally to contraction of Renal blood vessels in both mice and humans. Furthermore, preglomerular vascular SMCs and aortic SMCs coexpress L-, P-, and Q-type calcium channels within the same cell. Calcium channel blockers are widely used as pharmacological treatments. However, calcium channel antagonists vary in their selectivity for the various calcium channel subtypes, and the functional contribution from P/Q-type channels as compared with L-type should be considered. Confirming the presence of P/Q-type voltage-gated calcium channels in other types of vascular SMCs could be important when investigating phenomena such as hypertension, migraine, and other diseases known to involve SMCs and voltage-gated calcium channels. The purpose of this review was to give a short overview of the possible roles of P/Q-type calcium channels within the vascular system with special focus on the Renal Vasculature.
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Functional Importance of L- and P/Q-Type Voltage-Gated Calcium Channels in Human Renal Vasculature
Hypertension (Dallas Tex. : 1979), 2011Co-Authors: Pernille B. Lærkegaard Hansen, Christian Bo Poulsen, Steen Walter, Niels Marcussen, Leanne L. Cribbs, Ole Skøtt, Boye L. JensenAbstract:Calcium channel blockers are widely used for treatment of hypertension, because they decrease peripheral vascular resistance through inhibition of voltage-gated calcium channels. Animal studies of Renal Vasculature have shown expression of several types of calcium channels that are involved in kidney function. It was hypothesized that human Renal vascular excitation-contraction coupling involves different subtypes of channels. In human Renal artery and dissected intraRenal blood vessels from nephrectomies, PCR analysis showed expression of L-type (Ca(v) 1.2), P/Q-type (Ca(v) 2.1), and T-type subtype (Ca(v) 3.1 and Ca(v) 3.2) voltage-gated calcium channels (Ca(v)s), and quantitative PCR showed highest expression of L-type channels in Renal arteries and variable expression between patients of subtypes of calcium channels in intraRenal vessels. Immunohistochemical labeling of kidney sections revealed signals for Ca(v) 2.1 and Ca(v) 3.1 associated with smooth muscle cells of preglomerular and postglomerular vessels. In human intraRenal arteries, depolarization with potassium induced a contraction inhibited by the L-type antagonist nifedipine, EC(50) 1.2×10(-8) mol/L. The T-type antagonist mibefradil inhibited the potassium-induced constriction with large variations between patients. Interestingly, the P/Q-type antagonist, ω-agatoxin IVA, inhibited significantly the contraction with 24% at 10(-9) mol/L. In conclusion L-, P/Q, and T-type channels are expressed in human Renal blood vessels, and L- and P/Q-type channels are of functional importance for the depolarization-induced vasoconstriction. The contribution of P/Q-type channels to contraction in the human Vasculature is a novel mechanism for the regulation of Renal blood flow and suggests that clinical treatment with calcium blockers might affect vascular reactivity also through P/Q-type channel inhibition.
Roland E. Schmieder - One of the best experts on this subject based on the ideXlab platform.
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Rosuvastatin improves basal nitric oxide activity of the Renal Vasculature in patients with hypercholesterolemia
Atherosclerosis, 2007Co-Authors: Christian Ott, Bernhard Schmidt, Markus P. Schlaich, Stephanie Titze, Tim Schäufele, Roland E. SchmiederAbstract:Abstract Objective Impaired endothelium-dependent vasodilation represents an early manifestation of atherosclerosis. Prospective studies have demonstrated that impaired endothelial function in the peripheral circulation of hypercholesterolemic patients predicts CV events and can be restored by statin treatment. Whether this also holds true in the Renal circulation has not yet been adequately addressed. Methods In a double-blind, randomized, placebo-controlled cross-over trial, 40 hypercholesterolemic patients were randomly assigned to receive rosuvastatin (10mg/day) and matching placebo. The primary objective of the study was to assess the effect of 6-week treatment with rosuvastatin on basal NOS activity of the Renal Vasculature, as assessed by measuring Renal plasma flow (RPF) both before and after blockade of NOS with systemic infusion of N G -monomethyl-l-arginine (l-NMMA). In a subgroup of 20 patients we also studied the effects of a 3-day treatment regimen. Results Compared to placebo treatment, rosuvastatin decreased LDL-cholesterol levels both after 3 days and 6 weeks of treatment. The decrease in RPF in response to l-NMMA was significantly more pronounced after 6-week therapy with rosuvastatin compared to placebo (−13.7±1.0% versus −11.3±0.7%; p =0.046), indicating increased basal NOS activity with rosuvastatin treatment. A trend towards improved basal NOS activity was already evident after 3-day treatment. Conclusion Treatment with rosuvastatin improved basal NOS activity in the Renal circulation of hypercholesterolemic patients, suggestive of a nephroprotective effect. In view of the close relation between altered Renal function and cardiovascular events, these nephroprotective effects may contribute to the improved CV prognosis associated with statin treatment.
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Rapid Nongenomic Effects of Aldosterone on the Renal Vasculature in Humans
Hypertension (Dallas Tex. : 1979), 2006Co-Authors: Bernhard Schmidt, Ulla Sammer, Ingrid Fleischmann, Markus P. Schlaich, Christian Delles, Roland E. SchmiederAbstract:There is increasing evidence for the importance of rapid nongenomic effects of aldosterone on the human Vasculature. In vitro animal experiments in Renal arterioles also suggest the presence of such effects on the Renal Vasculature. We conducted a clinical study to explore these effects in vivo in humans. Thirteen healthy male volunteers were examined. Aldosterone (500 μg) or placebo was injected intravenously with or without coinfusion of N(G) monomethyl-l-arginine (l-NMMA) in a randomized, double-blinded 4-fold crossover design. Renal plasma flow and glomerular filtration rate were measured by constant infusion clearance technique using inulin and para -aminohippuric acid. Injection of aldosterone without concomitant infusion of l-NMMA changed the Renal plasma flow and glomerular filtration rate not statistically significant compared with placebo. Coinfusion of l-NMMA unmasked the effect of aldosterone: aldosterone with l-NMMA decreased the glomerular filtration rate slightly (−1.4±6.2 mL/min), whereas infusion of l-NMMA alone increased the glomerular filtration rate (8.3±9.8 mL/min; P =0.004). l-NMMA alone decreased Renal plasma flow by 58.2±97.5 mL/min, and aldosterone with l-NMMA decreased Renal plasma flow by 190.0±213.7 mL/min ( P =0.074). Accordingly, Aldosterone with l-NMMA increased Renal vascular resistance much more than l-NMMA alone (1588±237 versus 614±240 dyn×s×cm −5 ; P =0.014). These data indicate that aldosterone acts via rapid nongenomic effects in vivo in humans at the Renal Vasculature. Antagonizing the endothelial NO synthase unmasks these effects. Therefore, rapid nongenomic aldosterone effects increase Renal vascular resistance and thereby mediate arterial hypertension if endothelial dysfunction is present.
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Rapid nongenomic effects of aldosterone on the Renal Vasculature in humans. Commentary
Hypertension, 2006Co-Authors: Tae-yon Chun, Ulla Sammer, Ingrid Fleischmann, Markus P. Schlaich, Christian Delles, J. Howard Pratt, Bernhard M.w. Schmidt, Roland E. SchmiederAbstract:There is increasing evidence for the importance of rapid nongenomic effects of aldosterone on the human Vasculature. In vitro animal experiments in Renal arterioles also suggest the presence of such effects on the Renal Vasculature. We conducted a clinical study to explore these effects in vivo in humans. Thirteen healthy male volunteers were examined. Aldosterone (500 μg) or placebo was injected intravenously with or without coinfusion of N(G) monomethyl-L-arginine (L-NMMA) in a randomized, double-blinded 4-fold crossover design. Renal plasma flow and glomerular filtration rate were measured by constant infusion clearance technique using inulin and para-aminohippuric acid. Injection of aldosterone without concomitant infusion of L-NMMA changed the Renal plasma flow and glomerular filtration rate not statistically significant compared with placebo. Coinfusion of L-NMMA unmasked the effect of aldosterone: aldosterone with L-NMMA decreased the glomerular filtration rate slightly (-1.4±6.2 mL/min), whereas infusion of L-NMMA alone increased the glomerular filtration rate (8.3±9.8 mL/min; P=0.004). L-NMMA alone decreased Renal plasma flow by 58.2±97.5 mL/min, and aldosterone with L-NMMA decreased Renal plasma flow by 190.0±213.7 mL/min (P=0.074). Accordingly, Aldosterone with L-NMMA increased Renal vascular resistance much more than L-NMMA alone (1588±237 versus 614±240 dyn×s×cm -5 ; P=0.014). These data indicate that aldosterone acts via rapid nongenomic effects in vivo in humans at the Renal Vasculature. Antagonizing the endothelial NO synthase unmasks these effects. Therefore, rapid nongenomic aldosterone effects increase Renal vascular resistance and thereby mediate arterial hypertension if endothelial dysfunction is present.
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L-arginine-induced vasodilation of the Renal Vasculature is not altered in hypertensive patients with type 2 diabetes.
Diabetes care, 2003Co-Authors: Christian Delles, Markus P. Schneider, Sebastian Oehmer, Erwin H. Fleischmann, Roland E. SchmiederAbstract:OBJECTIVE —Diabetes, arterial hypertension, hypercholesterolemia, and aging are associated with endothelial dysfunction in various Vasculatures. Endothelium-dependent vasodilation of the Renal Vasculature cannot be easily assessed, but infusion of l-arginine, the substrate of endothelial nitric oxide synthase, leads to an increase in Renal plasma flow (RPF) in humans. We have examined the effect of l-arginine infusion on Renal hemodynamics in hypertensive patients with type 2 diabetes. RESEARCH DESIGN AND METHODS —Twenty-three elderly patients with type 2 diabetes (age, 65 ± 6 years; HbA 1c , 7.8 ± 1.6%) with coexisting arterial hypertension (158 ± 19/83 ± 11 mmHg) and elevated cholesterol levels (total cholesterol, 215 ± 33 mg/dl) were examined. These patients were compared with a young and healthy reference group ( n = 20; age, 26 ± 2 years). The effect of l-arginine infusion (100 mg/kg over 30 min) on RPF and glomerular filtration rate were measured using the constant input clearance technique with p -aminohippurate and inulin, respectively. RESULTS —l-Arginine infusion similarly influenced Renal hemodynamics in patients and reference subjects: RPF increased by 7 ± 11 and 7 ± 11% in diabetic and reference subjects, respectively ( P = NS). Other parameters of Renal hemodynamics such as glomerular filtration rate (5 ± 5 vs. 4 ± 4%) and filtration fraction (−1 ± 8 vs. −1 ± 9%) were not significantly different between diabetic and reference subjects, too. CONCLUSIONS —l-Arginine-induced vasodilation of the Renal Vasculature is not different between a group of hypertensive diabetic patients and a young, healthy reference group. These data were obtained using low-dose l-arginine infusion.
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Assessment of endothelial function of the Renal Vasculature in human subjects
American Journal of Hypertension, 2002Co-Authors: Christian Delles, Markus P. Schlaich, Johannes Jacobi, Stefan John, Roland E. SchmiederAbstract:Abstract Background l -Arginine, the substrate of nitric oxide (NO) synthase, and NG-monomethyl- l -arginine (L-NMMA), a competitive inhibitor of endothelial NO synthase, are used to analyze endothelial function of the Renal Vasculature. However, little is known about the appropriate dose of l -arginine to be used and the duration of action of l- arginine and L-NMMA. Methods Twenty-nine healthy male subjects (age, 27 ± 1 years) were examined. In protocol 1 (N = 17), l- arginine at low (100 mg/kg) and high dose (250 mg/kg), and high-dose l- arginine combined either with L-NMMA (total dose, 4.25 mg/kg; N = 9) or placebo (N = 8) were given. In protocol 2 (N = 12), L-NMMA was given before l- arginine infusion (100 mg/kg). Glomerular filtration rate (GFR) and Renal plasma flow (RPF) were measured at rest and at the end of each infusion step. Results In protocol 1, l- arginine dose dependently increased RPF and GFR (RPF: 599 ± 19 v 630 ± 18 v 690 ± 24 mL/min, P l- arginine 100 mg/kg and 250 mg/kg, respectively). However, these changes could not be antagonized by coinfusion of L-NMMA to l- arginine 250 mg/kg: RPF and GFR remained unchanged in both the placebo and the L-NMMA group. In protocol 2, L-NMMA decreased RPF (492 ± 18 v 567 ± 27 mL/min, P l- arginine (RPF: 533 ± 15 mL/min; GFR: 121 ± 4 mL/min; both parameters P = NS v L-NMMA and v baseline). Conclusions l -arginine at a dose of 100 mg/kg is sufficient to analyze endothelial function of the Renal Vasculature. The prolonged effect of L-NMMA and l- arginine must be taken into account in study protocols using both substances. Thus, stimulation and blockade of NO synthase cannot be examined in the same protocol.
Lale Umutlu - One of the best experts on this subject based on the ideXlab platform.
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new look at Renal Vasculature 7 tesla nonenhanced t1 weighted flash imaging
Journal of Magnetic Resonance Imaging, 2012Co-Authors: Lale Umutlu, Stefan Maderwald, Oliver Kraff, Sonja Kinner, Lc Schaefer, Karsten H. Wrede, Gerald Antoch, Michael Forsting, Mark E. Ladd, Thomas C. LauensteinAbstract:Purpose: To investigate the feasibility of 7 Tesla (T) nonenhanced high field MR imaging of the Renal Vasculature and to evaluate the diagnostic potential of various nonenhanced T1-weighted (T1w) sequences. Materials and Methods: Twelve healthy volunteers were examined on a 7T whole-body MR system (Magnetom 7T, Siemens Healthcare Sector) using a custom-built eight-channel radiofrequency (RF) transmit/receive body coil. Subsequent to RF shimming, the following sequences were acquired (i) fat-saturated two-dimensional (2D) FLASH, (ii) fat-saturated 3D FLASH, and a (iii) fat-saturated 2D time-of-flight MR angiography (TOF MRA). SNR and CNR were measured in the aorta and both Renal arteries. Qualitative analysis was performed with regard to vessel delineation (5-point scale: 5 = excellent to 1 = nondiagnostic) and presence of artifacts (5-point scale: 5 = no artifact present to 1 = strong impairment). Results: The inherently high signal intensity of the Renal arterial Vasculature in T1w imaging enabled moderate to excellent vessel delineation in all sequences. Qualitative (mean, 4.7) and quantitative analysis (SNRmean: 53.9; CNRmean: 28.0) demonstrated the superiority of TOF MRA, whereas 2D FLASH imaging provided poorest vessel delineation and was most strongly impaired by artifacts (overall impairment 3.7). The 3D FLASH MRI demonstrated its potential for fast high quality imaging of the nonenhanced arterial Vasculature, providing homogeneous hyperintense vessel signal. Conclusion: Nonenhanced T1w imaging in general and, TOF MRA in particular, appear to be promising techniques for good quality nonenhanced Renal artery assessment at 7 Tesla. J. Magn. Reson. Imaging 2012;36:714–721. © 2012 Wiley Periodicals, Inc.
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New look at Renal Vasculature: 7 tesla nonenhanced T1‐weighted FLASH imaging
Journal of magnetic resonance imaging : JMRI, 2012Co-Authors: Lale Umutlu, Stefan Maderwald, Oliver Kraff, Sonja Kinner, Lc Schaefer, Karsten H. Wrede, Gerald Antoch, Michael Forsting, Mark E. Ladd, Thomas C. LauensteinAbstract:Purpose: To investigate the feasibility of 7 Tesla (T) nonenhanced high field MR imaging of the Renal Vasculature and to evaluate the diagnostic potential of various nonenhanced T1-weighted (T1w) sequences. Materials and Methods: Twelve healthy volunteers were examined on a 7T whole-body MR system (Magnetom 7T, Siemens Healthcare Sector) using a custom-built eight-channel radiofrequency (RF) transmit/receive body coil. Subsequent to RF shimming, the following sequences were acquired (i) fat-saturated two-dimensional (2D) FLASH, (ii) fat-saturated 3D FLASH, and a (iii) fat-saturated 2D time-of-flight MR angiography (TOF MRA). SNR and CNR were measured in the aorta and both Renal arteries. Qualitative analysis was performed with regard to vessel delineation (5-point scale: 5 = excellent to 1 = nondiagnostic) and presence of artifacts (5-point scale: 5 = no artifact present to 1 = strong impairment). Results: The inherently high signal intensity of the Renal arterial Vasculature in T1w imaging enabled moderate to excellent vessel delineation in all sequences. Qualitative (mean, 4.7) and quantitative analysis (SNRmean: 53.9; CNRmean: 28.0) demonstrated the superiority of TOF MRA, whereas 2D FLASH imaging provided poorest vessel delineation and was most strongly impaired by artifacts (overall impairment 3.7). The 3D FLASH MRI demonstrated its potential for fast high quality imaging of the nonenhanced arterial Vasculature, providing homogeneous hyperintense vessel signal. Conclusion: Nonenhanced T1w imaging in general and, TOF MRA in particular, appear to be promising techniques for good quality nonenhanced Renal artery assessment at 7 Tesla. J. Magn. Reson. Imaging 2012;36:714–721. © 2012 Wiley Periodicals, Inc.
Taiji Matsusaka - One of the best experts on this subject based on the ideXlab platform.
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the cxcl12 sdf 1 cxcr4 axis is essential for the development of Renal Vasculature
Journal of The American Society of Nephrology, 2009Co-Authors: Yoshitsugu Takabatake, Taiji Matsusaka, Tatsuki Sugiyama, Hiroshi Kohara, Hidetake Kurihara, Pandelakis A. Koni, Yasuyuki Nagasawa, Takayuki Hamano, Isao MatsuiAbstract:CXC chemokine ligand 12 (CXCL12; stromal cell-derived factor 1) is a unique homeostatic chemokine that signals through its cognate receptor, CXCR4. CXCL12/CXCR4 signaling is essential for the formation of blood vessels in the gastrointestinal tract during development, but its contribution to Renal development remains unclear. Here, we found that CXCL12-secreting stromal cells surround CXCR4-positive epithelial components of early nephrons and blood vessels in the embryonic kidney. In glomeruli, we observed CXCL12-secreting podocytes in close proximity to CXCR4-positive endothelial cells. Both CXCL12- and CXCR4-deficient kidneys exhibited identical phenotypes; there were no apparent abnormalities in early nephrogenesis or in differentiation of podocytes and tubules, but there was defective formation of blood vessels, including ballooning of the developing glomerular tuft and disorganized patterning of the Renal Vasculature. To clarify the relative importance of different cellular defects resulting from ablation of CXCL12 and CXCR4, we established endothelial cell-specific CXCR4-deficient mice, which recapitulated the Renal phenotypes of conventional CXCR4-deficient mice. We conclude that CXCL12 secreted from stromal cells or podocytes acts on endothelial cells to regulate vascular development in the kidney. These findings suggest new potential therapeutic targets for remodeling the injured kidney.
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The CXCL12 (SDF-1)/CXCR4 axis is essential for the development of Renal Vasculature
Journal of the American Society of Nephrology : JASN, 2009Co-Authors: Yoshitsugu Takabatake, Taiji Matsusaka, Tatsuki Sugiyama, Hiroshi Kohara, Hidetake Kurihara, Pandelakis A. Koni, Yasuyuki Nagasawa, Takayuki Hamano, Isao Matsui, Noritaka KawadaAbstract:CXC chemokine ligand 12 (CXCL12; stromal cell-derived factor 1) is a unique homeostatic chemokine that signals through its cognate receptor, CXCR4. CXCL12/CXCR4 signaling is essential for the formation of blood vessels in the gastrointestinal tract during development, but its contribution to Renal development remains unclear. Here, we found that CXCL12-secreting stromal cells surround CXCR4-positive epithelial components of early nephrons and blood vessels in the embryonic kidney. In glomeruli, we observed CXCL12-secreting podocytes in close proximity to CXCR4-positive endothelial cells. Both CXCL12- and CXCR4-deficient kidneys exhibited identical phenotypes; there were no apparent abnormalities in early nephrogenesis or in differentiation of podocytes and tubules, but there was defective formation of blood vessels, including ballooning of the developing glomerular tuft and disorganized patterning of the Renal Vasculature. To clarify the relative importance of different cellular defects resulting from ablation of CXCL12 and CXCR4, we established endothelial cell-specific CXCR4-deficient mice, which recapitulated the Renal phenotypes of conventional CXCR4-deficient mice. We conclude that CXCL12 secreted from stromal cells or podocytes acts on endothelial cells to regulate vascular development in the kidney. These findings suggest new potential therapeutic targets for remodeling the injured kidney.
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Potent antihypertrophic effect of the bradykinin B2 receptor system on the Renal Vasculature
Kidney international, 1999Co-Authors: Shinya Tsuchida, Yoichi Miyazaki, Taiji Matsusaka, Tracy E. Hunley, Tadashi Inagami, Agnes B. Fogo, Iekuni IchikawaAbstract:Potent antihypertrophic effect of the bradykinin B2 receptor system on the Renal Vasculature. Background Angiotensin type 1 (AT1) receptor-deficient mice ( Agtr1 -/-), which selectively lack both AT1A and AT1B receptor genes, are characterized by marked intraRenal vascular thickening. In the present study, we explored the possible involvement of the kinin-kallikrein system in the development of this Renal vascular hypertrophy. Methods Wild-type and Agtr1 -/- mice were examined for the developmental regulation pattern of the kinin-kallikrein system and treated with aprotinin (a kallikrein inhibitor), AcLys [D-b Nal 7 , Ile 8 ] des-Arg 9 -bradykinin (a bradykinin B1 receptor antagonist), or Hoe-140 (a bradykinin B2 receptor antagonist) from 3 to 14 days of age. Results The normal postnatal up-regulation of kininase II was organ-specifically suppressed in Agtr1 -/- kidneys at 2 and 3 weeks of age. Immunohistochemical staining in Agtr1 -/- mice revealed tissue kallikrein staining along the nephron from connecting tubules to cortical collecting tubules in proximity to the hypertrophic Vasculature, whereas tissue kallikrein staining was confined to connecting tubules in wild-type mice. Aprotinin and Hoe-140 accelerated the vascular hypertrophy significantly as determined by wall thickness ratio, whereas B1 receptor antagonism had no effect. Conclusion The kinin-kallikrein system in the Agtr1 -/- mouse kidney is functionally activated by local suppression of kininase II and extensive redistribution of kallikrein to perivascular areas. This activation, specific to the kidney, serves to dampen a development of the marked vascular hypertrophy. These results demonstrate, to our knowledge for the first time, the antihypertrophic effect of the bradykinin B2 receptor system on the Renal Vasculature in vivo.