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Genetic Deletion of P2Y 2 Receptor Induces Vascular Endothelial Dysfunction but not Large Artery Stiffening in Mice
Author(s) -
Kishore B K,
Henson GD,
Zhang Y,
Carlson NG,
Lesniewski LA,
Donato A J
Publication year - 2015
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.29.1_supplement.803.5
Subject(s) - vasodilation , medicine , endocrinology , endothelial dysfunction , vasoconstriction , endothelium , nitric oxide , sodium nitroprusside , receptor , vascular smooth muscle , chemistry , smooth muscle
The G‐protein coupled and UTP/ATP‐sensitive P2Y 2 receptor has been linked to production of nitric oxide (NO) and prostaglandins in numerous cell types including endothelial and vascular smooth muscle cells. We hypothesized that genetic deletion of P2Y 2 would induce generalized dysfunction in arteries. We measured endothelium dependent dilation to acetylcholine (ACh) in the presence or absence of the NO inhibitor, L‐NAME, in large central (carotid) and small peripheral (gastrocnemius feed) arteries (N = 15) isolated from 5 – 8 months old P2Y 2 deficient (‐/‐) or wild type (WT) mice. Maximal vasodilation to ACh was blunted in both carotid (Car) and gastrocnemius (Gas) feed arteries in the P2Y 2 ‐/‐ compared to WT (Car: 88 ± 1 vs. 97 ± 2%; Gast: 86 ± 3 vs. 97 ± 2%; both p<0.05). L‐NAME significantly reduced vasodilation in arteries from both groups (p<0.05), but abolished differences between P2Y 2 ‐/‐ and WT, indicating blunted NO dependent dilation in P2Y 2 ‐/‐ arteries. Smooth muscle function, assessed by dilation to sodium nitroprusside, was similar between P2Y 2 ‐/‐ and WT (Car: 98 ± 1 vs. 95 ± 2%; Gast: 91 ± 3 vs. 90 ± 2%; both p>0.05). Despite endothelial dysfunction in P2Y 2 ‐/‐ mice, in vivo large artery stiffness assessed via pulse wave velocity was similar between groups (p>0.05). Thus, deletion of the P2Y 2 receptor induces endothelial dysfunction and reduces NO bioavailability in large and small arteries but does not impact smooth muscle vasodilation or large artery stiffness.