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Decreased alpha‐2B‐adrenoceptor (α 2B ‐AR) expression augments nitric oxide (NO) dependent dilation
Author(s) -
Cherng Tom W.,
Duling Laura C.,
Griego Jason R.,
Kanagy Nancy L.
Publication year - 2006
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.20.5.a1184-d
Subject(s) - mesenteric arteries , enos , phenylephrine , vasodilation , constriction , medicine , endocrinology , nitric oxide synthase , vasoconstriction , cyclooxygenase , chemistry , nitric oxide , anatomy , artery , blood pressure , enzyme , biochemistry
Mice heterozygous for a non‐functional α 2B ‐AR (Het) are more susceptible to NO synthase‐inhibition hypertension than wild type (WT) mice. Furthermore, Het mice have augmented NO‐dependent vasodilation and increased vascular expression of endothelial NOS (eNOS). We hypothesized that this increased eNOS inhibits both myogenic and agonist‐stimulated tone in arteries from Het mice. In isolated, pressurized mesenteric arteries (inner diameter = 170±3 μm), myogenic tone was not different between groups in untreated arteries. NOS‐inhibition (L‐NNA, 10 −4 mol/L) increased myogenic tone more in Het arteries than in WT arteries PE constriction of mesenteric arteries. * different between groups. # (15±3% Het versus 5±3% WT; p <0.05). Phenylephrine (PE, 10 −5 mol/L) constricted Het arteries less than WT arteries ( Figure). However, in L‐NNA treated arteries, PE constriction was not different between Het and WT arteries. In contrast, cyclooxygenase (COX) inhibition (indomethacin, 10 −5 mol/L) decreased PE constriction only in WT arteries. COX inhibition was reversed by L‐NNA, suggesting COX products inhibit NO production in WT but not Het arteries. Therefore arteries from Het mice (with decreased α 2B ‐AR expression) have diminished myogenic and α 1 ‐AR‐induced constriction that is apparently caused by increased NO‐mediated dilation. In agreement with our previous observation that COX inhibition increases NO production in mesenteric arteries, the augmented NO dilation in Het arteries appears to be caused in part by loss of COX‐dependent inhibition of NOS.(Supported by AHA Established Investigator award and EPA RD‐83186001, NLK)