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

Abstract

Citation: Otani S, Nagaoka T, Omae T, et al. Histamine-induced dilation of isolated porcine retinal arterioles: role of endothelium-derived hyperpolarizing factor. Invest Ophthalmol Vis Sci. 2016;57:4791-4798. DOI:10.1167/iovs.15-19038 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 lM) 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 (N G -nitro-L-arginine methyl ester, L-NAME), or Ca 2þ -activated K þ (K Ca ) 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 K Ca channel activation, in addition to the endothelial release of NO and prostanoids.

Role of Arginase in Selective Impairment of Endothelium-Dependent Nitric Oxide Synthase-Mediated Dilation of Retinal Arterioles during Early Diabetes

“…25,44 In contrast, we also have shown that histamine-induced dilation of porcine retinal arterioles is dependent on activation of both NOS and COX. 37 The present findings corroborate these earlier results by showing that the NOS inhibitor L-NAME attenuated the dilation of retinal arterioles from control nondiabetic pigs to histamine (Fig. 1), supporting the role of NO in this vasodilation.…”

“…This in vitro approach allowed us to directly assess the endothelial NOS and COX pathways. We used two endogenous vasodilator agonists, histamine 37 , 41 – 43 and bradykinin, 25 , 44 as pharmacologic tools to assess endothelial function of retinal arterioles. Histamine and bradykinin may exert a local impact on regulation of retinal arteriolar tone based on the existence of histamine-generating enzymes and the kallikrein-kinin system in the retinal tissue of several vertebrates including human.…”

“…Cannulated and pressurized arterioles were bathed in PSS-albumin at 36°C to 37°C to allow the development of basal tone (stable within 90 minutes). To evaluate the effect of diabetes on vasomotor function, endothelium-dependent vasodilation to histamine (0.1 to 30 µmol/L) 37 and bradykinin (1 pmol/L to 10 nmol/L) 25 were established in vessels isolated from the diabetic and euglycemic control pigs. Vessels were exposed to each concentration of agonist for 2 to 3 minutes until a stable diameter was maintained.…”

“…Vessels were exposed to each concentration of agonist for 2 to 3 minutes until a stable diameter was maintained. The roles of NOS and COX in vasodilations were examined using the specific inhibitor N G -nitro-L-arginine methyl ester (L-NAME, 10 µmol/L, 40-minute incubation) 37 , 38 and indomethacin (10 µmol/L, 40-minute incubation), 35 , 37 respectively. For some vessels, the relationship between NOS and arginase in the vasodilations to histamine and bradykinin was evaluated in the presence of L-NAME with or without the arginase inhibitor nor-NOHA (0.1 mmol/L intraluminal treatment for 90 minutes; Cayman Chemical; Ann Arbor, MI, USA).…”

Functional Interaction among KCa and TRP Channels for Cardiovascular Physiology: Modern Perspectives on Aging and Chronic Disease

“…The majority of the work delineating the individual contributions of SK Ca and IK Ca channels to vasodilation and tissue hyperemia was performed using mesenteric (gut) arteries as an accessible and abundant source of resistance arteries in the body [56,57,58]. However, to a lesser extent, studies also resolved clear contributions of respective K Ca channel subtypes in the microcirculation of the eye [59], brain [60,61,62], heart [63,64], lung [65,66], skeletal muscle [8,67], and kidney [68,69,70]. While it is clear that both SK Ca and IK Ca channels are integral to overall cardiovascular health (systemic vascular resistance and blood pressure control), respective K Ca contributions underlying hyperemia throughout organs may vary.…”