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NO‐dependent Molecular Mechanism in Relaxing Effect of Cilnidipine (CIL) in Human Internal Mammary Arteries (IMA)
Author(s) -
Fan Li,
Xiao Xiaoqiu,
Grove Kevin,
Huang Yu,
Yang Qin,
Furnary Anthony,
He GuoWei
Publication year - 2008
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.22.1_supplement.1128.10
Subject(s) - enos , chemistry , bradykinin , guanosine , endocrinology , endothelium , medicine , nitric oxide , stimulation , cyclic guanosine monophosphate , messenger rna , incubation , nitric oxide synthase , receptor , biochemistry , gene
CIL, the novel long‐lasting L/N‐type dihydropyridine calcium channel blocker, induces both endothelium‐dependent and independent relaxation in human IMA. We investigated the underlying molecular mechanism on nitric oxide (NO)‐cyclic guanosine monophosphate (cGMP) pathway. The expression level of eNOS mRNA in IMA incubated with/without (n=5/6) 3 μ CIL for 30 min followed by 10 μM norepinephrine (NE) stimulation for 4 hrs was assayed by Real‐Time quantitative PCR. The phosphorylation of eNOS at Ser 1177 (p‐eNOS) was determined by Western blotting in IMA (n=4) simulated by 10 μM NE for 15 min followed by incubation for 5 min with 3 μM CIL or 50 nM bradykinin. The CIL‐induced relaxation was examined in endothelium‐denuded (n=7) and ‐intact IMA (n=7) pretreated with/without LNNA (300 μM, n=8) and ODQ (3 μM, n=8). CIL 3 μM increased eNOS mRNA expression by 42.4% and p‐eNOS by 55.0% in the NE‐stimulated IMA. Endotheliumdenudation (47.7 ± 7.0%, p < 0.05), L‐NNA (48.6 ± 6.1%, p < 0.05), and ODQ (41.6 ± 3.8%, p < 0.01) remarkably reduced the CIL‐induced relaxation to 40 mM K + ‐induced contraction, comparing to endothelium‐intact control (73.9 ± 6.4 %). Thus, CIL‐induced endothelium‐dependent relaxation in human IMA is mediated by NOcGMP signal pathway with strong molecular evidence. Supported by St. Vincent Foundation, Hong Kong RGC (CUHK4383/03M) & CUHK (4450171, 4450231, 2041305).