Histamine-Induced Dilation of Isolated Porcine Retinal Arterioles: Role of Endothelium-Derived Hyperpolarizing Factor.
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.



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.



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.



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.
Department of Ophthalmology Asahikawa Medical University, Asahikawa, Japan.
Shinichi
S
Otani
Department of Ophthalmology Asahikawa Medical University, Asahikawa, Japan.
Taiji
T
Nagaoka
Department of Ophthalmology Asahikawa Medical University, Asahikawa, Japan.
Tsuneaki
T
Omae
Department of Ophthalmology Asahikawa Medical University, Asahikawa, Japan.
Ichiro
I
Tanano
Department of Ophthalmology Asahikawa Medical University, Asahikawa, Japan.
Takayuki
T
Kamiya
Department of Ophthalmology Asahikawa Medical University, Asahikawa, Japan.
Shinji
S
Ono
Department of Ophthalmology, Scott & White Eye Institute, Temple, Texas, United States 3Department of Surgery, College of Medicine, Texas A&M Health Science Center, Temple, Texas, United States.
Travis W
TW
Hein
Department of Ophthalmology, Scott & White Eye Institute, Temple, Texas, United States 3Department of Surgery, College of Medicine, Texas A&M Health Science Center, Temple, Texas, United States 4Department of Medical Physiology, College of Medicine, Texas A&M Health Science Center, Temple, Texas, United States.
Lih
L
Kuo
Department of Ophthalmology Asahikawa Medical University, Asahikawa, Japan.
Akitoshi
A
Yoshida
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001685:Biological Factors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D012171:Retinal Vessels / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D006632:Histamine