Histamine exerts its effects by binding to its four receptors, H1, H2, H3, and H4, on target cells in various tissues.
16 In vasculatures, depending upon species and tissue types, Ottosson et al.
49 have reported that histamine-induced dilation in small human temporal arteries is mediated by both H1 and H2 receptors. In guinea-pig pulmonary arteries, the dilation to histamine is mediated by H1 receptors.
50 On the other hand, H2 receptors mediate the dilation of canine spinal arteries to histamine.
51 In bovine retinal arteries, the dilation is reported to be mediated mainly by H1 with small contribution from H2 receptors.
19 However, in the current study, we found that the H2-receptor antagonist famotidine was more effective than H1-blocker chlorpheniramine in inhibiting histamine-induced vasodilation (
Fig. 3). In addition, combined administration of chlorpheniramine and famotidine abolished the histamine-induced response. Our data suggest that H2 receptors play a dominant role in the dilation of small porcine retinal arterioles to histamine. The role of H3 and H4 receptors appears to be minimal because inhibition of H3 and H4 receptors by thioperamide had no effect on the vasodilation to histamine (
Fig. 3). The discrepancy between previous bovine (H1 dominant)
19 and current porcine (H2 dominant) study on retinal vascular dilation to histamine is unclear. The different approaches (the pressurized vascular segment versus stretched vascular ring), the development of vascular tone (spontaneous basal tone versus external preconstrictor), vessel size (∼100 vs. 250 μm), and species difference (porcine versus bovine) may contribute to the observed inconsistent results. Interestingly, in healthy humans, histamine dilates retinal arteries and veins in a manner sensitive to H1-receptor antagonist diphenhydramine
24 but not to H2-blocker cimetidine.
23 However, the role of H2 receptors cannot be completely excluded because the efficacy of cimetidine in blocking H2 receptors in the above human study has not been tested.
23 Our finding on the prominent role of H2 receptors in mediating retinal arteriolar dilation is consistent with the finding in human ophthalmic arteries.
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