Vascular ENaC proteins are required for renal myogenic constriction

Jernigan, Nikki L.; Drummond, Heather A.

doi:10.1152/ajprenal.00019.2005

Cited by 131 publications

(177 citation statements)

References 47 publications

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“…This occurs via dilation or constriction in response to alterations in blood pressure, which incite changes in circumferential wall tension. The active myogenic response closely follows an initial passive distension, as has been observed in a multitude of experimental studies (5,11,19,26,27,30,32,39,45,58,61,63).…”

Section: Vessel Modelsupporting

confidence: 69%

“…The active data (5,19,22,26,27,29,64) were subsequently examined to determine the shape and position of the sigmoidal dependence between tension and VSM activation, providing values for C t i and CЈ t i . An iterative bisection method was used for each Strahler order to determine the sigmoidal relationships between MRss and Ttot that, when incorporated into the mathematical system, minimized the error in vessel diameter responses between the model predictions and the experimental results (5,19,22,26,27,29,64).…”

Section: Parameter Determinationmentioning

confidence: 99%

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Dynamic myogenic autoregulation in the rat kidney: a whole-organ model

Kleinstreuer¹,

Todem²,

Plank³

et al. 2008

American Journal of Physiology-Renal Physiology

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Kleinstreuer N, David T, Plank MJ, Endre Z. Dynamic myogenic autoregulation in the rat kidney: a whole-organ model. Am J Physiol Renal Physiol 294: F1453-F1464, 2008. First published March 19, 2008 doi:10.1152/ajprenal.00426.2007.-A transient 1D mathematical model of whole-organ renal autoregulation in the rat is presented, examining the myogenic response on multiple levels of the renal vasculature. Morphological data derived from micro-CT imaging were employed to divide the vasculature via a Strahler ordering scheme. A previously published model of the myogenic response based on wall tension is expanded and adapted to fit the response of each level, corresponding to a distally dominant resistance distribution with the highest contributions localized to the afferent arterioles and interlobular arteries. The mathematical model was further developed to include the effects of in vivo viscosity variation and flow-induced dilation via endothelial nitric oxide production. Computer simulations of the autoregulatory response to pressure perturbations were examined and compared with experimental data. The model supports the hypothesis that change in circumferential wall tension is the catalyst for the myogenic response. The model provides a basis for examining the steady state and transient characteristics of the whole-organ renal myogenic response in the rat, as well as the modulatory influences of metabolic and hemodynamic factors.renal; myogenic response THE MYOGENIC RESPONSE, a pressure-induced constriction or dilation of the vasculature first discovered 100 years ago by Bayliss, is now known to exist throughout the body (28). It is crucial in establishing basal arterial tone and maintaining a relatively constant blood supply to major organs, a phenomenon known as autoregulation (13). There are two key autoregulatory mechanisms in the kidney, the tubuloglomerular feedback (TGF) loop, which monitors NaCl delivery and filtration rate and adjusts afferent arteriolar resistance accordingly, and the myogenic response, which is the focus of current research and exists to varying degrees throughout the renal vasculature. Together, these two mechanisms account for ϳ90% of renal autoregulation, with 50% attributed to the myogenic component (30,31,39). The estimation of this regulatory balance is based on an assumed linearity of the system and is subject to variations due to observed nonlinear interactions among mechanisms (41,42,62). Other possible mechanisms, with less impact and longer time courses, could be attributed to metabolic catalysts, sympathetic stimulation, or various other causes.The myogenic response features predominantly in the small arteries and arterioles which make up the majority of peripheral resistance in the vasculature; this adjusts the vascular smooth muscle (VSM) tone, and hence diameter, to provide dynamic regulation of blood flow. The cellular mechanisms by which the myogenic response operates have been extensively studied (13,23,26,50,52). There is general agreement that an alteration in circumf...

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Section: Vessel Modelsupporting

confidence: 69%

Section: Parameter Determinationmentioning

confidence: 99%

Dynamic myogenic autoregulation in the rat kidney: a whole-organ model

Kleinstreuer¹,

Todem²,

Plank³

et al. 2008

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…In addition, other genes either with or without a heterozygous CFTR genotype could produce the "nonclassic" CF phenotype in the absence of homozygous CFTR mutation as shown previously (Groman et al, 2002). Recently, it was shown that an ENaC gene (SCNN1) produced a non-classical CF phenotype (Sheridan et al, 2005) and ENaC was shown previously to be involved in stretch-induced muscle constriction (Jernigan and Drummond, 2005).…”

Section: Discussionmentioning

confidence: 80%

Cystic fibrosis transmembrane conductance regulator (CFTR) dependent cytoskeletal tension during lung organogenesis

Cohen

Larson

2006

Developmental Dynamics

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There is growing evidence for the role of CFTR (cystic fibrosis transmembrane conductance regulator) in lung development and differentiation. The mechanism by which the chloride channel could affect lung organogenesis, however, is unknown. In utero CFTR gene transfer in the fetal lungs of mice, rats, and non-human primates was shown previously to alter lung structure and function. A study of the genes altered in the fetal rat lung following CFTR overexpression was initiated in an effort to determine the molecular mechanism for CFTR-dependent differentiation. In utero gene transfer with recombinant adenoviruses carrying either a reporter gene or CFTR resulted in the increased expression of a number of genes upon microarray analysis. The majority of the genes overexpressed in the CFTR-treated lungs were primarily associated with muscle structure and function. Histological and biochemical characterization of these proteins including myosin heavy chain, heat shock protein 27, and isoforms of myosin light chain showed that CFTR overexpression had a profound effect on smooth muscle contraction-related proteins. The CFTR-dependent regulation of smooth muscle contraction related proteins was shown to be related to chloride and extracellular ATP and was dependent upon the PI3 Kinase and Phospholipase C pathways. The changes in smooth muscle proteins were consistent with CFTR-dependent contractions of the embryonic airway smooth muscle. An assay was developed using fluorescent polystyrene beads to show that CFTR did indeed increase amniotic fluid flow into the fetal lung. Increased amniotic fluid pressure was shown previously to be associated with stretch-induced differentiation of the lung. Evaluation of neonatal respiratory function showed that CFTR-dependent muscle contractions and increased amniotic fluid pressure resulted in accelerated maturation of the neonatal rat lung. In addition, these CFTR-dependent changes were shown to be sufficient to reverse the lung phenotype of the CFTR knockout mouse. Mechanical forces influence lung development through pulmonary distension. CFTR overexpression in the fetal lung altered differentiation and development in the lung. These results are consistent with CFTR influencing lung development by regulating the muscle contractions associated with cytoskeletal tension and stretch induced differentiation. Deficiency of CFTR altering lung development would contribute significantly to the Cystic Fibrosis disease phenotype.

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“…The expressions of ENaC and related acid-sensing ion channel (ASIC) have been demonstrated in cerebral arterial myocytes, and suggested to play a role in MRs (Carattino et al, 2004;Jernigan and Drummond, 2005). However, it is not confirmed in other types arteries, and we could not detect any attenuation of MRs by amiloride (up to 10 M, unpublished data).…”

Section: Epithelial Na + Channel (Enac)mentioning

confidence: 70%

Mechanisms of myogenic response: Ca2+-dependent and -independent signaling

Baek¹,

Kim

2011

J. Smooth Muscle Res.

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In many organs, blood flow is maintained at a relatively constant level although pressure changes substantially. This autoregulation of blood flow is achieved in several ways including the myogenic response (MR). MR is triggered by mechanical stretch of vascular smooth muscle. Activation of stretch activated channels (SACs) on vascular smooth muscle cells induces depolarization, Ca -sensitizing signals seem to be variable depending on the types of arteries as well as animal species. Finally, impaired MRs are related in various pathological conditions, such as hypertension, stroke and diabetes mellitus. Therefore, identification of MR signaling mechanism might be a target of treatment in vascular diseases.

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Vascular ENaC proteins are required for renal myogenic constriction

Cited by 131 publications

References 47 publications

Dynamic myogenic autoregulation in the rat kidney: a whole-organ model

Dynamic myogenic autoregulation in the rat kidney: a whole-organ model

Cystic fibrosis transmembrane conductance regulator (CFTR) dependent cytoskeletal tension during lung organogenesis

Mechanisms of myogenic response: Ca2+-dependent and -independent signaling

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