scholarly journals Lack of Connexins 40 and 45 Reduces Local and Conducted Vasoconstrictor Responses in the Murine Afferent Arterioles

2020 ◽  
Vol 11 ◽  
Author(s):  
Sophie Møller ◽  
Jens Christian Brings Jacobsen ◽  
Niels-Henrik Holstein-Rathlou ◽  
Charlotte M. Sorensen
Keyword(s):  
Afferent Arterioles

The role of osmolarity in renin release from afferent arterioles

1989 ◽  
Vol 7 (9) ◽  
pp. 757???762 ◽  
Author(s):  
Bao M. Twu ◽  
Michael E. Cannon ◽  
Chen H. Hsu
Keyword(s):  
Renin Release ◽  
Afferent Arterioles

scholarly journals Potassium channel contributions to afferent arteriolar tone in normal and diabetic rat kidney

2008 ◽  
Vol 295 (1) ◽  
pp. F171-F178 ◽  
Author(s):  
Carmen M. Troncoso Brindeiro ◽  
Rachel W. Fallet ◽  
Pascale H. Lane ◽  
Pamela K. Carmines
Keyword(s):  
Potassium Channel ◽  
Rat Kidney ◽  
The Other ◽  
Diabetic Rat ◽  
Channel Blockers ◽  
Juxtamedullary Nephron ◽  
Afferent Arterioles ◽  
Arteriolar Tone ◽  
Constrictor Response

We previously reported an enhanced tonic dilator impact of ATP-sensitive K+ channels in afferent arterioles of rats with streptozotocin (STZ)-induced diabetes. The present study explored the hypothesis that other types of K+ channel also contribute to afferent arteriolar dilation in STZ rats. The in vitro blood-perfused juxtamedullary nephron technique was utilized to quantify afferent arteriolar lumen diameter responses to K+ channel blockers: 0.1–3.0 mM 4-aminopyridine (4-AP; KV channels), 10–100 μM barium (KIR channels), 1–100 nM tertiapin-Q (TPQ; Kir1.1 and Kir3.x subfamilies of KIR channels), 100 nM apamin (SKCa channels), and 1 mM tetraethylammonium (TEA; BKCa channels). In kidneys from normal rats, 4-AP, TEA, and Ba2+ reduced afferent diameter by 23 ± 3, 8 ± 4, and 18 ± 2%, respectively, at the highest concentrations employed. Neither TPQ nor apamin significantly altered afferent diameter. In arterioles from STZ rats, a constrictor response to TPQ (22 ± 4% decrease in diameter) emerged, and the response to Ba2+ was exaggerated (28 ± 5% decrease in diameter). Responses to the other K+ channel blockers were similar to those observed in normal rats. Moreover, exposure to either TPQ or Ba2+ reversed the afferent arteriolar dilation characteristic of STZ rats. Acute surgical papillectomy did not alter the response to TPQ in arterioles from normal or STZ rats. We conclude that 1) KV, KIR, and BKCa channels tonically influence normal afferent arteriolar tone, 2) KIR channels (including Kir1.1 and/or Kir3.x) contribute to the afferent arteriolar dilation during diabetes, and 3) the dilator impact of Kir1.1/Kir3.x channels during diabetes is independent of solute delivery to the macula densa.

Angiotensin II Ca2+ signaling in rat afferent arterioles: stimulation of cyclic ADP ribose and IP3 pathways

2005 ◽  
Vol 288 (4) ◽  
pp. F785-F791 ◽  
Author(s):  
Susan K. Fellner ◽  
William J. Arendshorst
Keyword(s):  
Calcium Release ◽  
Rat Kidney ◽  
Ang Ii ◽  
High Concentration ◽  
Inositol Trisphosphate Receptor ◽  
Cyclic Adp Ribose ◽  
Specific Antagonist ◽  
Afferent Arterioles ◽  
Trisphosphate Receptor ◽  
Calcium Induced Calcium Release

ANG II induces a rise in cytosolic Ca2+ ([Ca2+]i) in vascular smooth muscle (VSM) cells via inositol trisphosphate receptor (IP3R) activation and release of Ca2+ from the sarcoplasmic reticulum (SR). The Ca2+ signal is augmented by calcium-induced calcium release (CICR) and by cyclic adeninediphosphate ribose (cADPR), which sensitizes the ryanodine-sensitive receptor (RyR) to Ca2+ to further amplify CICR. cADPR is synthesized from β-nicotinamide adenine dinucleotide (NAD+) by a membrane-bound bifunctional enzyme, ADPR cyclase. To investigate the possibility that ANG II activates the ADPR cyclase of afferent arterioles, we used inhibitors of the IP3R, RyR, and ADPR cyclase. Afferent arterioles were isolated from rat kidney with the magnetized microsphere and sieving technique and loaded with fura-2 to measure [Ca2+]i. In Ca2+-containing buffer, ANG II increased [Ca2+]i by 125 ± 10 nM. In the presence of the IP3R antagonists TMB-8 and 2-APB, the peak responses to ANG II were reduced by 74 and 81%, respectively. The specific antagonist of cADPR 8-Br ADPR and a high concentration of ryanodine (100 μM) inhibited the ANG II-induced increases in [Ca2+]i by 75 and 69%, respectively. Nicotinamide and Zn2+ are known inhibitors of the VSM ADPR cyclase. Nicotinamide diminished the [Ca2+]i response to ANG II by 66%. In calcium-free buffer, Zn2+ reduced the ANG II response by 68%. Simultaneous blockade of the IP3 and cADPR pathways diminished the [Ca2+]i response to ANG II by 83%. We conclude that ANG II initiates Ca2+ mobilization from the SR in afferent arterioles via the classic IP3R pathway and that ANG II may lead to activation of the ADPR cyclase to form cADPR, which, via its action on the RyR, substantially augments the Ca2+ response.

Abstract 261: Endothelial Cells Contribute to RAS Activation in Microvascular Smooth Muscle Cells

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Kayoko Miyata ◽  
Ryousuke Satou ◽  
L Gabriel Navar
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Mrna Expression ◽  
Culture Medium ◽  
Primary Cultures ◽  
Mrna Levels ◽  
Ang Ii ◽  
Relative Ratio ◽  
Renin Mrna ◽  
Afferent Arterioles

Introduction: We have demonstrated that Ang II augments angiotensinogen (AGT) expression in rat preglomerular vascular smooth muscle cells (VSMCs). However, it is unclear if endothelial cells (ECs) are involved in augmentation of AGT in renal afferent arterioles. Hypothesis: We assessed the hypothesis that the ECs respond to paracrine signals that Ang II contribute to AGT augmentation in VSMCs. Objective: We established primary cultures of preglomerular ECs and examined the effects of Ang II and/or culture medium from ECs on AGT expression in preglomerular VSMCs. Methods and Results: We established primary cultures of preglomerular ECs, isolated from afferent arterioles of Sprague-Dawley rats. The cells were identified as ECs by being positive for a marker, CD34 and endothelial NOS and negative for alpha-SMA (a marker for VSMCs) and P4H-b (a marker for Fibroblasts) by immnostaining. The expression levels of AGT mRNA and renin mRNA in preglomerular ECs were examined by real-time RT-PCR. Ang II (100 pmol/L) increased AGT mRNA levels (1.34 +/- 0.16, by 100 pmol/L, N=4) and Renin mRNA levels (6.16 +/- 0.96, by 100 nmol/L, N=4) in ECs. On the other hand, the same dose of Ang II suppressed Renin mRNA expression in isolated Juxtaglomerular cells (JGs). These results indicate that preglomerular ECs are respond to Ang II and exclude the possible contamination of JGs into ECs. 100 pmol/L of Ang II increased AGT mRNA expression levels (1.37 +/- 0.03, relative ratio, N=4) in preglomerular VSMCs and the culture medium of ECs without Ang II treatment also more increased AGT mRNA expression (1.62 +/- 0.13, relative ratio, N=4) in preglomerular VSMCs. The AGT mRNA expression augmentation was enhanced when preglomerular VSMCs were treated with culture medium of Ang II-treated preglomerular ECs (2.39 +/- 0.41, relative ratio, N=4). The synergistic effects of Ang II and preglomerular ECs were also observed in PAI-1 expression in preglomerular VSMCs. Conclusion: These data demonstrate that preglomerular ECs contribute to Ang II-upregulation of AGT in renal afferent arterioles leading to further Ang II augmentation, which leads to increases in inflammatory and sclerotic factors in preglomerular VSMCs.

Angiotensin II effects on microvascular diameters of in vitro blood-perfused juxtamedullary nephrons

1986 ◽  
Vol 251 (4) ◽  
pp. F610-F618 ◽  
Author(s):  
P. K. Carmines ◽  
T. K. Morrison ◽  
L. G. Navar
Keyword(s):  
Angiotensin Ii ◽  
Constant Pressure ◽  
Ang Ii ◽  
Experimental Conditions ◽  
Vasoactive Hormones ◽  
Juxtamedullary Nephron ◽  
Single Nephron ◽  
Afferent Arterioles ◽  
Dose Dependent

The purpose of this study was to determine the specific renal microvascular segments that are functionally responsive to angiotensin II (ANG II) and other vasoactive hormones. Experiments were performed on juxtamedullary tissue from captopril-treated rats during perfusion with blood at a constant pressure of 110 mmHg. Epifluorescence videomicroscopy was utilized to measure diameters of arcuate and interlobular arteries (ART), mid- (MA) and late- (LA) afferent arterioles, and efferent arterioles (EA). Norepinephrine (700 nM) significantly decreased, and sodium nitroprusside (380 nM) increased, inside diameters of all segments. Topical application of ANG II (0.01 to 1 nM) induced significant reductions in diameters of all vessel segments: ART, 17.5 +/- 2.0%; MA, 19.6 +/- 2.5%; LA, 13.5 +/- 1.5%; and EA, 16.9 +/- 2.7%. The preglomerular response to ANG II was blocked by saralasin (10 microM) and, in most cases, was dose dependent; however, an initial hypersensitivity to low ANG II doses (30% decrease in diameter) was exhibited by 38% of the preglomerular vessels studied. Under these experimental conditions, single-nephron glomerular filtration rate decreased significantly in response to 0.01 nM ANG II exposure. These observations demonstrate that physiological concentrations of ANG II can elicit receptor-dependent and reversible vasoconstriction of the juxtamedullary nephron microvasculature at both pre- and postglomerular sites.

Modulation of vascular tone in renal microcirculation by erythrocytes: role of EDRF

1993 ◽  
Vol 264 (1) ◽  
pp. H190-H195 ◽  
Author(s):  
J. D. Imig ◽  
D. Gebremedhin ◽  
D. R. Harder ◽  
R. J. Roman
Keyword(s):  
Vascular Tone ◽  
Physiological Salt Solution ◽  
Nitric Oxide Synthase Inhibitor ◽  
Renal Microcirculation ◽  
Vasoconstrictor Response ◽  
A Cell ◽  
Afferent Arterioles ◽  
Synthase Inhibitor

The effect of erythrocytes (red blood cells, RBC) on vascular tone in the renal microcirculation was examined using the juxtamedullary nephron microvascular preparation perfused in vitro with a physiological salt solution containing 5% albumin. The basal diameters of the arcuate, interlobular, proximal, and distal afferent arterioles averaged 444 +/- 24, 74 +/- 3, 29 +/- 1, and 19 +/- 1 micron, respectively, when perfused with a cell-free solution at a pressure of 80 mmHg. The diameters of the arcuate and interlobular arteries increased by 14 +/- 4 and 13 +/- 4%, respectively, whereas the diameter of the proximal and distal portions of the afferent arterioles decreased by 7 +/- 2% when perfusion pressure was elevated from 80 to 160 mmHg. The addition of RBC to the perfusate reduced the basal diameters of interlobular and afferent arterioles by 11 +/- 4 and 15 +/- 3%, respectively. The maximal vasoconstrictor response was seen after the addition of only 1% RBC to the perfusate. Removal of platelets did not block the vasoconstrictor response to addition of RBC to the perfusate. The role of endothelium-derived relaxing factor (EDRF) in the vasoconstrictor response to RBC was studied by addition of nitric oxide synthase inhibitor, N omega-nitro-L-arginine (L-NNA, 100 microM) to the perfusate. L-NNA reduced the basal diameters of interlobular and afferent arterioles by 7 +/- 3 and 9 +/- 3%, respectively, and abolished the vasoconstrictor response to RBC. L-NNA had no effect on the pressure-diameter relationships of the preglomerular vasculature when added to perfusates already containing RBC.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Rapid Inhibition of Vasoconstriction in Renal Afferent Arterioles by Aldosterone

2003 ◽  
Vol 93 (12) ◽  
pp. 1258-1266 ◽  
Author(s):  
T.R. Uhrenholt ◽  
J. Schjerning ◽  
P.B. Hansen ◽  
R. Nørregaard ◽  
B.L. Jensen ◽  
...  
Keyword(s):  
Afferent Arterioles

Abstract 070: Canonical Wnt Signaling Mediates Enhanced Renal Afferent Arteriolar Reactive Oxygen Species and Contractility in Diabetic Mice

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
En Yin Lai ◽  
Suping Zhang ◽  
Qian Huang ◽  
Qiaoling Wang ◽  
Liang Zhao ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Wnt Signaling ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Diabetic Mice ◽  
Canonical Wnt Signaling ◽  
Protein Expressions ◽  
Afferent Arterioles ◽  
Gsk 3Β ◽  
Canonical Wnt

Background: Canonical Wnt signaling is involved in oxidative stress and diabetes but its role in diabetic renal microvascular dysfunction is unclear. We tested the hypothesis that enhanced canonical Wnt signaling in renal afferent arterioles from diabetic mice increases reactive oxygen species (ROS) and contractions to endothelin-1 (ET-1). Methods: Diabetic or control C57Bl/6 mice received vehicle or sulindac (40 mg·kg -1 ·day -1 ) to block canonical Wnt signaling for 4 weeks. ET-1 contractions were measured in diameter changes and H 2 O 2 and O 2 .- by fluorescence microscopy. Arteriolar protein expression and enzymatic activity were examined by standard methods. Results: Compared to control, diabetic mouse afferent arteriole had significantly increased O 2 .- (+84%) and H 2 O 2 (+91%) and enhanced sensitivity to ET-1 at 10 -8 mol·l -1 (-72±4% versus -43±4%, P<0.05) accompanied by significantly (P<0.005) reduced protein expressions and activities for catalase and superoxide dismutase 2 (SOD2). Incubation of afferent arterioles from normal or diabetic mice with PEG-SOD reduced responses to ET-1 whereas incubation with PEG-catalase reduced sensitivity to ET-1 selectively in arterioles from diabetic mice. The arteriolar protein expressions for canonical Wnt signaling indicated overactivation of this pathway in diabetic mice (2.6-fold increase in p-GSK-3β/GSK-3β and 3.3-fold decrease in p-β-catenin/β-catenin). Sulindac given to diabetic mice normalized the canonical Wnt signaling protein and arteriolar O 2 .- , H 2 O 2 and ET-1 contractions while doubling (P<0.05) microvascular catalase and SOD2. Conclusions: Increased ROS, notably H 2 O 2 , mediated by canonical Wnt signaling contributes to enhanced afferent arteriolar sensitivity to ET-1 in diabetes. Thus, antioxidant pharmacological strategies targeting canonical Wnt signaling may improve vascular function in diabetic nephropathy.

Abstract P266: Thromboxane-prostanoid Receptors (tp-rs) Mediate Hypertension, H2o2 Generation and Impaired Renal Afferent Arteriolar Myogenic Responses Leading to Nephropathy in Doca/salt Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Christopher S Wilcox ◽  
Lingli Li ◽  
En Yin Lai ◽  
Adam Hosszu ◽  
William J Welch
Keyword(s):  
Blood Pressure ◽  
Perfusion Pressure ◽  
High Salt ◽  
Myogenic Tone ◽  
Prostanoid Receptors ◽  
Hypertensive Nephropathy ◽  
Sham Treatment ◽  
H2o2 Generation ◽  
Afferent Arterioles ◽  
Myogenic Responses

Background: DOCA/uninephrectomy/high salt (DOCA) is a model of hypertensive nephropathy. Afferent arteriolar myogenic responses prevent hypertensive renal barotrauma but myogenic tone is blocked by vascular generation of H 2 O 2 . Since thromboxane-prostanoid receptors (TP-Rs) generate H 2 O 2 , we tested the hypothesis that they mediate hypertensive nephropathy. Methods: DOCA and Sham TP-R +/+ and -/- mice (n=6/group) were studied at 2 weeks and myogenic responses recorded from the diameter of perfused single afferent arterioles studied in a bath preparation during increased perfusion pressure (40 to 80 mmHg). Results: DOCA treatment in TP-R +/+ mice increased (p<0.001) 24-hour excretion of H 2 O 2 (45 ± 3 vs 220 + 15 nmol) , TxB 2 (4 ± 2 vs 29 ± 4 pmol) and albumin (20 ± 5 vs 270 ± 20 mg) and increased MAP by 35 ± 5 mmHg. However, all effects of DOCA were prevented in TP-R -/- mice. Sham treatment had no effect in TPR +/+ or -/- mice. Myogenic responses were severely impaired in DOCA vs sham WT mice (Δ diameter: -4 ± 1 vs -8 ± 1%; p< 0.005). Myogenic responses also were reduced by incubation of arterioles with 10 -10 mol·l -1 of the TP-R mimetic, U-46,619 vs vehicle added to the bath for 10 minutes (Δ diameter: -7 ± 1 vs -10 ± 1%; p<0.01) and in WT mice infused for 3 days with U-46,619 (500 ng·kg -1 ·d -1 x 3) vs vehicle (Δ diameter: -3 ± 1 vs -10 ± 1%; p<0.005). Conclusion: Hypertensive nephropathy is dependent on TP-Rs that mediate the increase in H 2 O 2 and blood pressure and likely the impaired myogenic responses that expose the kidney to barotrauma

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