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Vasoactive intestinal peptide‐induced relaxation is mediated by nitric oxide activation in the endothelial caveolae of rat aorta
Author(s) -
HillPryor Crystal Darlene,
Linder A. Elizabeth,
Linder Felipe,
Leite Romulo
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.20.4.a721-b
Subject(s) - vasoactive intestinal peptide , caveolae , nitric oxide , enos , phenylephrine , endocrinology , vasodilation , chemistry , medicine , endothelium , nitric oxide synthase , aorta , biology , biochemistry , neuropeptide , signal transduction , receptor , blood pressure
Vasoactive intestinal peptide (VIP) a non‐adrenergic non‐cholinergic (NANC) transmitter widely distributed in both the central and peripheral nervous system is an endothelium‐dependent vasodilator. The contribution of endothelium derived relaxing factors to VIP‐induced relaxation remains unclear. We hypothesized that nitric oxide (NO) produced by endothelial NO synthase (eNOS) at the caveolae plays a role in this relaxation. We assessed the effect of VIP on isolated rat aorta rings in vitro which was incubated with either N‐nitro‐L‐Arginine, L‐NNA, (a NOS inhibitor), indomethacin (a cycloxygenase inhibitor), or methyl‐beta‐cyclodextrin (a membrane sequester that disassembles caveolae). In intact and denuded aortic rings precontracted with phenylephrine (PE, 0.1 μmol/L), the addition of VIP (1nmol/L to 1 μmol/L) produced relaxation in a dose‐dependent manner. The maximal relaxation induced by VIP in endothelium‐intact aortic rings (53 ± 9%, n=8) was impaired after removal of the endothelium (11 ± 2%, n=3, P<0.05), or in the presence of L‐NNA (20 ± 11%, n=5, P <0.05) and methyl‐β‐cyclodextrin (20 ± 8%, n=6, P<0.05). In contrast, VIP‐induced relaxation was enhanced in the presence of indomethacin (83 ± 7%, n=5, P<0.05). These data suggest that NO produced by eNOS at the caveolae plays a stimulatory role in VIP‐induced relaxation in rat aorta, whereas prostaglandins play an inhibitory role.