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Histamine-Induced Dilation of Isolated Porcine Retinal Arterioles: Role of Endothelium-Derived Hyperpolarizing Factor
- Source :
- Investigative ophthalmology and visual science. 57(11):4791-4798
- Publication Year :
- 2016
-
Abstract
- This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.<br />PURPOSE: Although endothelium-dependent nitric oxide (NO)-mediated dilation of retinal arterioles has been well described, the role of endothelium-derived hyperpolarizing factor (EDHF) in the retinal arteriolar response remains unclear. In the current study, we examined the contribution of EDHF to the retinal arteriolar dilation to the inflammatory agent histamine and investigated the signaling mechanisms underlying this vasomotor activity. METHODS: Porcine retinal arterioles were isolated, cannulated, and pressurized without flow for functional study by using video microscopic techniques. The immunohistochemical staining was performed to determine histamine receptor subtypes. RESULTS: Histamine (0.1-30 μM) produced concentration-dependent dilation of retinal arterioles in a manner sensitive to H1- and H2-receptor antagonists chlorpheniramine and famotidine, respectively. Histamine-induced vasodilation was almost abolished after endothelial removal. In the intact vessels, vasodilation to histamine was partially inhibited by the inhibitors of cyclooxygenase (indomethacin), NO synthase (NG-nitro-L-arginine methyl ester, L-NAME), or Ca2+ -activated K+ (KCa) channels (apamin plus charybdotoxin). Combination of the above inhibitors abolished histamine-induced vasodilation. Residual vasodilation in the presence of indomethacin and L-NAME was further reduced by the cytochrome P450 enzyme inhibitor sulfaphenazole but not by the gap junction inhibitor carbenoxolone or the hydrogen peroxide scavenger catalase. Immunohistochemical signals for H1- and H2-receptor expression were found only in the endothelium. CONCLUSIONS: The endothelium plays an essential role in the dilation of porcine retinal arterioles to histamine via H1- and H2-receptor activation. The EDHF derived from cytochrome P450 contributed in part to this vasodilation via KCa channel activation, in addition to the endothelial release of NO and prostanoids.
- Subjects :
- 0301 basic medicine
Male
Endothelium-derived hyperpolarizing factor
Endothelium
Swine
Vasodilation
030204 cardiovascular system & hematology
Pharmacology
Apamin
Muscle, Smooth, Vascular
Nitric oxide
03 medical and health sciences
Histamine receptor
chemistry.chemical_compound
Biological Factors
0302 clinical medicine
medicine
Animals
Retinal Vessels
Retinal
Immunohistochemistry
Arterioles
030104 developmental biology
medicine.anatomical_structure
chemistry
cardiovascular system
Female
Endothelium, Vascular
Histamine
Subjects
Details
- Language :
- English
- ISSN :
- 01460404
- Volume :
- 57
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Investigative ophthalmology and visual science
- Accession number :
- edsair.doi.dedup.....ba786f7eebba70b715e8d25286114f6b