Zoltan Nemeth1, Michael J Ryan2, Joey P Granger1, Heather A Drummond1. 1. Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA. 2. Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, South Carolina, USA.
Abstract
BACKGROUND: Pressure-induced constriction (PIC) is inherent to small arteries and arterioles, in which intraluminal pressure-induced vascular smooth muscle cell stretch elicits vasoconstriction. Degenerin (Deg) proteins, such as beta-epithelial Na+ channel (βENaC), have been studied in the PIC response because they are evolutionarily linked to known mechanosensors. While loss of Deg function phenotypes are plentiful, a gain-of-function phenotype has not been studied. The aim of this study was to determine if expression of exogenous βENaC in the isolated middle cerebral artery (MCA) enhances the PIC response. METHODS: Isolated MCA segments from female mice (24 weeks, n = 5) were transfected with enhanced green fluorescent protein-βENaC (EGFP-βENaC) or with EGFP alone, incubated overnight at 37 °C, then studied in a pressure myograph. RESULTS: Mechanical/morphological properties and vasoconstrictor responses to KCl and phenylephrine were identical in EGFP-βENaC and EGFP MCAs. In contrast, PIC responses were greater in EGFP-βENaC segments with ~2-fold greater peak myogenic tone. CONCLUSIONS: These data confirm previous findings that βENaC is critical in the PIC response. These data provide proof-of-concept that upregulating βENaC can enhance PIC responses and lay the foundation to test the hypothesis that inflammation-mediated downregulation of βENaC contributes to cerebrovascular dysfunction.
BACKGROUND: Pressure-induced constriction (PIC) is inherent to small arteries and arterioles, in which intraluminal pressure-induced vascular smooth muscle cell stretch elicits vasoconstriction. Degenerin (Deg) proteins, such as beta-epithelial Na+ channel (βENaC), have been studied in the PIC response because they are evolutionarily linked to known mechanosensors. While loss of Deg function phenotypes are plentiful, a gain-of-function phenotype has not been studied. The aim of this study was to determine if expression of exogenous βENaC in the isolated middle cerebral artery (MCA) enhances the PIC response. METHODS: Isolated MCA segments from female mice (24 weeks, n = 5) were transfected with enhanced green fluorescent protein-βENaC (EGFP-βENaC) or with EGFP alone, incubated overnight at 37 °C, then studied in a pressure myograph. RESULTS: Mechanical/morphological properties and vasoconstrictor responses to KCl and phenylephrine were identical in EGFP-βENaC and EGFP MCAs. In contrast, PIC responses were greater in EGFP-βENaC segments with ~2-fold greater peak myogenic tone. CONCLUSIONS: These data confirm previous findings that βENaC is critical in the PIC response. These data provide proof-of-concept that upregulating βENaC can enhance PIC responses and lay the foundation to test the hypothesis that inflammation-mediated downregulation of βENaC contributes to cerebrovascular dysfunction.
Authors: Jeremy W Duncan; Subhi Talal Younes; Emily Hildebrandt; Michael J Ryan; Joey P Granger; Heather A Drummond Journal: Am J Physiol Heart Circ Physiol Date: 2020-03-13 Impact factor: 4.733
Authors: Rhian M Touyz; Rheure Alves-Lopes; Francisco J Rios; Livia L Camargo; Aikaterini Anagnostopoulou; Anders Arner; Augusto C Montezano Journal: Cardiovasc Res Date: 2018-03-15 Impact factor: 10.787