Connexin45 Cannot Replace the Function of Connexin40 in Conducting Endothelium-Dependent Dilations Along Arterioles

Wölfle, Stephanie E.; Schmidt, Volker; Hoepfl, Bernd; Gebert, Andreas; Alcoléa, Sébastien; Gros, Daniël; Wit, Cor de

doi:10.1161/circresaha.107.163279

Cited by 85 publications

(114 citation statements)

References 38 publications

(51 reference statements)

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“…Moreover, Cx40 deficiency impairs only conduction of vasodilator but not vasoconstrictor signals. 3,4,23 Replacement of Cx40 by Cx45, regulated by the Cx40 promoter, improves the defects in autoregulation and TGF but does not completely restore them to normal. The reason why Cx45 only partially replaces the function of Cx40 in the JGA is not known.…”

Section: Discussionmentioning

confidence: 99%

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Connexin 40 Mediates the Tubuloglomerular Feedback Contribution to Renal Blood Flow Autoregulation

Just

Kurtz

Wit

et al. 2009

Journal of the American Society of Nephrology

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Connexins are important in vascular development and function. Connexin 40 (Cx40), which plays a predominant role in the formation of gap junctions in the vasculature, participates in the autoregulation of renal blood flow (RBF), but the underlying mechanisms are unknown. Here, Cx40-deficient mice (Cx40-ko) had impaired steady-state autoregulation to a sudden step increase in renal perfusion pressure. Analysis of the mechanisms underlying this derangement suggested that a marked reduction in tubuloglomerular feedback (TGF) in Cx40-ko mice was responsible. In transgenic mice with Cx40 replaced by Cx45, steady-state autoregulation and TGF were weaker than those in wild-type mice but stronger than those in Cx40-ko mice. N-Nitro-L-arginine-methyl-ester (L-NAME) augmented the myogenic response similarly in all genotypes, leaving autoregulation impaired in transgenic animals. The responses of renovascular resistance and arterial pressure to norepinephrine and acetylcholine were similar in all groups before or after L-NAME inhibition. Systemic and renal vasoconstrictor responses to L-NAME were also similar in all genotypes. We conclude that Cx40 contributes to RBF autoregulation by transducing TGF-mediated signals to the afferent arteriole, a function that is independent of nitric oxide (NO). However, Cx40 is not required for the modulation of the renal myogenic response by NO, norepinephrine-induced renal vasoconstriction, and acetylcholine-or NO-induced vasodilation.

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Section: Discussionmentioning

confidence: 99%

“…20,21 Gap junctions are also implicated in vasodilation, 14,22 although it is unclear whether or not Cx40 is involved. 3,14,23 Few studies have tested the participation of connexins in vasodilation in vivo. 5,14 To our knowledge, no data exist regarding connexins in vasoconstrictor responses in an animal.…”

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confidence: 99%

Connexin 40 Mediates the Tubuloglomerular Feedback Contribution to Renal Blood Flow Autoregulation

Just

Kurtz

Wit

et al. 2009

Journal of the American Society of Nephrology

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“…The major breakthrough entailed opening the muscle, detaching it from the testicle and spreading it radially as a flat sheet for transillumination under a compound microscope 4 . While shown to be a valuable preparation to study the physiology of the microcirculation in rats 5 and hamsters 6 , the cremaster muscle in mice 7 has proven particularly useful in dissecting cellular pathways involved in regulating microvascular function [8][9][10][11] and real-time imaging of intercellular signaling 12 .…”

Section: Introductionmentioning

confidence: 99%

The Mouse Cremaster Muscle Preparation for Intravital Imaging of the Microcirculation

Bagher

Segal

2011

JoVE

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Throughout the body, the maintenance of homeostasis requires the constant supply of oxygen and nutrients concomitant with removal of metabolic by-products. This balance is achieved by the movement of blood through the microcirculation, which encompasses the smallest branches of the vascular supply throughout all tissues and organs. Arterioles branch from arteries to form networks that control the distribution and magnitude of oxygenated blood flowing into the multitude of capillaries intimately associated with parenchymal cells. Capillaries provide a large surface area for diffusional exchange between tissue cells and the blood supply. Venules collect capillary effluent and converge as they return deoxygenated blood towards the heart. To observe these processes in real time requires an experimental approach for visualizing and manipulating the living microcirculation.The cremaster muscle of rats was first used as a model for studying inflammation using histology and electron microscopy post mortem 1,2 . The first in vivo report of the exposed intact rat cremaster muscle investigated microvascular responses to vasoactive drugs using reflected light 3 . However curvature of the muscle and lack of focused illumination limited the usefulness of this preparation. The major breakthrough entailed opening the muscle, detaching it from the testicle and spreading it radially as a flat sheet for transillumination under a compound microscope 4 . While shown to be a valuable preparation to study the physiology of the microcirculation in rats 5 and hamsters 6 , the cremaster muscle in mice 7 has proven particularly useful in dissecting cellular pathways involved in regulating microvascular function [8][9][10][11] and real-time imaging of intercellular signaling 12 .The cremaster muscle is derived from the internal oblique and transverse abdominus muscles as the testes descend through the inguinal canal 13. It serves to support (Greek: cremaster = suspender) and maintain temperature of the testes. As described here, the cremaster muscle is prepared as a thin flat sheet for outstanding optical resolution. With the mouse maintained at a stable body temperature and plane of anesthesia, surgical preparation involves freeing the muscle from surrounding tissue and the testes, spreading it onto transparent pedestal of silastic rubber and securing the edges with insect pins while irrigating it continuously with physiological salt solution. The present protocol utilizes transgenic mice expressing GCaMP2 in arteriolar endothelial cells. GCaMP2 is a genetically encoded fluorescent calcium indicator molecule 12 . Widefield imaging and an intensified charge-coupled device camera enable in vivo study of calcium signaling in the arteriolar endothelium. Video LinkThe video component of this article can be found at https://www.jove.com/video/2874/ Protocol 1. Mouse board, muscle pedestal, body wedge and superfusion solution 1. Mouse board: A transparent rectangular Plexiglas board (6" wide X 8" long X 3/16" thick) is made to fit on the...

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“…Regional functional changes in the renal cortex infl uence the resulting function of the system and changes in renal function were related to microcirculation, membrane receptors, transporting channels and cell organelles (5,7,10). Renal performance is regulated by signal molecules and infl uenced by organ, tissue, cell and molecular interactions (12).…”

Section: Discussionmentioning

confidence: 99%

“…Mechanical transduction activates transcription and mediator release, inducing local and systemic infl ammatory reactions having adverse effects on kidney function (2,7,10). The renal cortical microcirculation is regulated by connexins (12) while endogenous catecholamine directly affects regional perfusion (8,14). Aldosterone affects ion excretion and activates the renin-angiotensin system by induction of angiotensin converting enzyme expression (7,15).…”

Section: Discussionmentioning

confidence: 99%

Reduction of renal function during mechanical ventilation of healthy lungs in an animal biomodel

Kobr¹,

Fremuth²,

Šašek³

et al. 2015

BLL

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Abstract:Objectives: To identify factors involved in reno-pulmonary interactions during mechanical ventilation. Materials and methods:The study included a total of 25 domestic piglets. The animals were divided into three groups based on different strategies of ventilation. Group A; spontaneously breathing piglets; group B animals ventilated with tidal volume of 6 ml.kg -1 and group C with animals ventilated with tidal volume 10 ml.kg -1 . Clinical monitoring and laboratory tests were performed for all groups at baseline and then at 1 hour and 12 hours for groups B and C. Ventilation indices, hemodynamics, urine output, creatinine clearance, glomerular fi ltration index, fractional excretion of sodium, free water clearance and tissue samples were recorded. The data obtained were statistically analysed. Results: Lower creatinine clearance and renal indices were seen in group B (p < 0.05) and in group C (p < 0.001) at 1 hour, and a difference in urine output for group C (p < 0.01) compared to group A was observed. At 12 hours, there was a further reduction in creatinine clearance and renal indices for group B (p < 0.05) and group C (p < 0.01). The lung mechanics and hemodynamics were not signifi cantly infl uenced. Conclusions:The study showed a causal relationship between renal dysfunction and positive pressure mechanical ventilation with respect to tidal volume and time (Tab. 4, Fig. 2, Ref. 17). Text in PDF www.elis.sk.

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Connexin45 Cannot Replace the Function of Connexin40 in Conducting Endothelium-Dependent Dilations Along Arterioles

Cited by 85 publications

References 38 publications

Connexin 40 Mediates the Tubuloglomerular Feedback Contribution to Renal Blood Flow Autoregulation

Connexin 40 Mediates the Tubuloglomerular Feedback Contribution to Renal Blood Flow Autoregulation

The Mouse Cremaster Muscle Preparation for Intravital Imaging of the Microcirculation

Reduction of renal function during mechanical ventilation of healthy lungs in an animal biomodel

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