Contractile Force Is Enhanced in Aortas from Pendrin Null Mice Due to Stimulation of Angiotensin II-Dependent Signaling

Sutliff, Roy L.; Walp, Erik R.; Kim, Young Hee; Walker, Lori A.; El-Ali, Alexander; Ma, Jing; Bonsall, Robert W.; Ramosevac, Semra; Eaton, Douglas C.; Verlander, Jill W.; Hansen, Laura; Gleason, Rudolph L.; Pham, Truyen D.; Hong, Seongun; Pech, Vladimir; Wall, Susan M.

doi:10.1371/journal.pone.0105101

Cited by 9 publications

(13 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While we did not observe pendrin expression in vascular tissue, pendrin gene ablation increased thoracic aorta contractile force in response to either ␣-adrenergic agonists (phentolamine) or angiotensin II (75). This increment in contractile force is associated with increased abundance of myosin light chain kinase 20 and is eliminated with the administration of angiotensin type 1a receptor inhibitors (candesartan) in vivo (75). Since epinephrine and norepinephrine are ␣-adrenergic agonists, the increased vascular contractility observed in response to ␣-adrenergic agonists and angiotensin II may limit the hypotension observed in pendrin null mice.…”

Section: Does Pendrin Modulate Blood Pressure Solely Through Its Acticontrasting

confidence: 90%

“…Since blood pressure is the product of cardiac output and systemic vascular resistance, we explored the effect of pendrin gene ablation on vascular tone (75). While we did not observe pendrin expression in vascular tissue, pendrin gene ablation increased thoracic aorta contractile force in response to either ␣-adrenergic agonists (phentolamine) or angiotensin II (75). This increment in contractile force is associated with increased abundance of myosin light chain kinase 20 and is eliminated with the administration of angiotensin type 1a receptor inhibitors (candesartan) in vivo (75).…”

Section: Does Pendrin Modulate Blood Pressure Solely Through Its Actimentioning

confidence: 60%

“…Since epinephrine and norepinephrine are ␣-adrenergic agonists, the increased vascular contractility observed in response to ␣-adrenergic agonists and angiotensin II may limit the hypotension observed in pendrin null mice. However, because pendrin is expressed at low levels in vascular tissue, such as the thoracic aorta, pendrin gene ablation likely enhances the force of contraction through an indirect effect, such as through changes in circulating levels or angiotensin II and/or catecholamines (75).…”

Section: Does Pendrin Modulate Blood Pressure Solely Through Its Actimentioning

confidence: 99%

See 2 more Smart Citations

The role of pendrin in blood pressure regulation

Wall

2016

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

Pendrin is a Na(+)-independent Cl(-)/HCO3(-) exchanger found in the apical regions of type B and non-A, non-B intercalated cells within the aldosterone-sensitive region of the nephron, i.e., the distal convoluted tubule (DCT), the connecting tubule (CNT), and the cortical collecting duct (CCD). Type B intercalated cells mediate Cl(-) absorption and HCO3(-) secretion primarily through pendrin-mediated Cl(-)/HCO3(-) exchange. This exchanger is upregulated with angiotensin II administration and in models of metabolic alkalosis, such as following administration of aldosterone or NaHCO3. In the absence of pendrin-mediated HCO3(-) secretion, an enhanced alkalosis is observed following aldosterone or NaHCO3 administration. However, probably of more significance is the role of pendrin in the pressor response to aldosterone. Pendrin mediates Cl(-) absorption and modulates aldosterone-induced Na(+) absorption mediated by the epithelial Na channel (ENaC). Pendrin changes ENaC activity by changing both channel open probability (Po) and surface density (N), at least partly by altering luminal HCO3(-) and ATP concentration. Thus aldosterone and angiotensin II stimulate pendrin expression and function, which stimulates ENaC activity, thereby contributing to the pressor response of these hormones. However, pendrin may modulate blood pressure partly through its extrarenal effects. For example, pendrin is expressed in the adrenal medulla, where it modulates catecholamine release. The increase in catecholamine release observed with pendrin gene ablation likely contributes to the increment in vascular contractile force observed in the pendrin null mouse. This review summarizes the signaling mechanisms that regulate pendrin abundance and function as well as the contribution of pendrin to distal nephron function.

show abstract

Section: Does Pendrin Modulate Blood Pressure Solely Through Its Acticontrasting

confidence: 90%

Section: Does Pendrin Modulate Blood Pressure Solely Through Its Actimentioning

confidence: 60%

Section: Does Pendrin Modulate Blood Pressure Solely Through Its Actimentioning

confidence: 99%

See 1 more Smart Citation

The role of pendrin in blood pressure regulation

Wall

2016

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Since blood pressure is the product of systemic vascular resistance and cardiac output, we had explored the effect of pendrin gene ablation on vascular tone [ 96 ]. Although we did not observe pendrin expression in vascular tissue, pendrin gene ablation increased thoracic aorta contractile force in response to either α adrenergic agonists (phentolamine) or angiotensin II [ 96 ]. This greater contractile force was associated with increased myosin light chain kinase 20 abundance and was eliminated when an angiotensin type 1a receptor inhibitor, i.e.…”

Section: Does Pendrin Regulate Blood Pressure Through a Mechanism Thamentioning

confidence: 99%

“…This greater contractile force was associated with increased myosin light chain kinase 20 abundance and was eliminated when an angiotensin type 1a receptor inhibitor, i.e. candesartan, was given in vivo [ 96 ]. This increased vascular contractility may also limit the hypotension that follows pendrin gene ablation.…”

Section: Does Pendrin Regulate Blood Pressure Through a Mechanism Thamentioning

confidence: 99%

Renal intercalated cells and blood pressure regulation

Wall

2017

Kidney Res Clin Pract.

Self Cite

View full text Add to dashboard Cite

Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl− absorption and HCO3− secretion largely through pendrin-dependent Cl−/HCO3− exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO3 administration. In some rodent models, pendrin-mediated HCO3− secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl− absorption, but also by modulating the aldosterone response for epithelial Na+ channel (ENaC)-mediated Na+ absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure.

show abstract

Vascular contractile reactivity in hypotension due to reduced renal reabsorption of Na+ and restricted dietary Na+

Alshahrani

Rapoport

Soleimani

2017

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

Reduced renal Na reabsorption along with restricted dietary Na depletes intravascular plasma volume which can then result in hypotension. Whether hypotension occurs and the magnitude of hypotension depends in part on compensatory angiotensin II-mediated increased vascular resistance. We investigated whether the ability of vascular resistance to mitigate the hypotension was compromised by decreased contractile reactivity. In vitro reactivity was investigated in aorta from mouse models of reduced renal Na reabsorption and restricted dietary Na associated with considerable hypotension and renin-angiotensin system activation: (1) the Na-Cl-Co-transporter (NCC) knockout (KO) with Na restricted diet (0.1%, 2 weeks) and (2) the relatively more severe pendrin (apical chloride/bicarbonate exchanger) and NCC double KO. Contractile sensitivity to KCl, phenylephrine, and/or U46619 remained unaltered in aorta from both models. Maximal KCl and phenylephrine contraction expressed as force/aorta length from NCC KO with Na-restricted diet remained unaltered, while in pendrin/NCC double KO were reduced to 49 and 64%, respectively. Wet weight of aorta from NCC KO with Na-restricted diet remained unaltered, while pendrin/NCC double KO was reduced to 67%, consistent with decreased medial width determined with Verhoeff-Van Gieson stain. These findings suggest that hypotension associated with severe intravascular volume depletion, as the result of decreased renal Na reabsorption, may in part be due to decreased contractile reactivity as a consequence of reduced vascular hypertrophy.

show abstract

Contractile Force Is Enhanced in Aortas from Pendrin Null Mice Due to Stimulation of Angiotensin II-Dependent Signaling

Cited by 9 publications

References 43 publications

The role of pendrin in blood pressure regulation

The role of pendrin in blood pressure regulation

Renal intercalated cells and blood pressure regulation

Vascular contractile reactivity in hypotension due to reduced renal reabsorption of Na+ and restricted dietary Na+

Contact Info

Product

Resources

About