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Acid Sensing Ion Channel 1 Contributes to Endothelium‐Dependent Vasodilation in Mesenteric Arteries
Author(s) -
Garcia Selina,
Herbert Lindsay,
Resta Thomas C,
Jernigan Nikki L
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1281.7
Subject(s) - vasoconstriction , vasodilation , phenylephrine , mesenteric arteries , medicine , anesthesia , cardiology , artery , endocrinology , blood pressure
Our laboratory has previously shown that acid sensing ion channel 1 (ASIC1) is expressed in pulmonary arterial smooth muscle and contributes to agonist‐induced Ca 2+ influx and vasoconstriction. However, the contribution of ASIC1 to vasoreactivity in the systemic circulation is unknown. To address this question, we simultaneously measured changes in arterial wall Ca 2+ and inner diameter in response to increasing concentrations of phenylephrine (PE; 10 −8 ‐10 −5 M) or endothelin‐1 (ET‐1; 10 −11 – 10 −8 M) in isolated, pressurized mesenteric resistance arteries. To examine the role of ASIC1 in agonist‐induced vasoconstriction, these experiments were completed in the presence or absence of the selective ASIC1 antagonist, psalmotoxin 1 (PcTX1; 20 nM), applied either abluminally or to both luminal and abluminal surfaces of the artery. Inhibition of ASIC1 did not alter PE‐induced vasoconstriction, but augmented vasoconstriction in response to lower concentrations of ET‐1 when PcTX1 was present in the lumen. These data suggest that, in contrast to vasoconstrictor actions of ASIC1 in the pulmonary circulation, ASIC1 limits agonist‐induced vasoconstriction in the systemic circulation. Therefore, we hypothesized that endothelial expression of ASIC1 contributes to mesenteric arterial dilation. To test this hypothesis, mesenteric arteries were pre‐constricted to ~50% of baseline inner diameter with the thromboxane analog, U‐46619 (10 −7 M), and vasodilatory responses to increasing concentrations of acetylcholine Ach (ACh; 10 −9 ‐ 10 −5 M) were assessed in the presence or absence of PcTX1 in the lumen. ACh‐induced vasodilation was significantly blunted in the presence of PcTX1. We conclude that ASIC1 contributes to endothelium‐dependent vasodilation in mesenteric arteries. These data demonstrate differing roles of ASIC1 in regulation of pulmonary and systemic vasoreactivity. Support or Funding Information NIH NHLBI ROI HL111084 (N.L. Jernigan) NIH NHLBI T32 HL007736 (B.R. Walker)