Role of histamine H1 and H2 receptor antagonists in the prevention of intimal thickening

Norio Miyazawa, Shinji Watanabe, Akihisa Matsuda, Kazunao Kondo, Hisakuni Hashimoto, Kazuo Umemura, Mitsuyoshi Nakashima

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)


Vascular smooth muscle cell migration to the intima from the media and proliferation in the intima play key roles in atherosclerosis and restenosis after coronary angioplasty. Histamine released from adherent platelets at the injured artery and from mast cells in atheromas has stimulant actions on both smooth muscle cell migration and proliferation, and histamine receptor antagonists abolish the effect of histamine in vitro. The aim of this study was to examine the effect of histamine receptor antagonists on intimal thickening. Endothelial injury in the mouse femoral artery was induced by a photochemical reaction between localized irradiation by green light and intravenously administered rose bengal. The histamine H1 receptor antagonist, diphenhydramine, at a dose of 30 mg/kg or the histamine H2 receptor antagonist, cimetidine, at a dose of 200 mg/kg was intraperitoneally administered to mice for 21 days after endothelial injury. Twenty-one days after endothelial injury, morphometric analysis was performed to measure the cross-sectional areas of the intima and media. Diphenhydramine significantly reduced the intimal area to 1.1±0.3 (x10-3 mm2) compared with the value in the control group, which was 6.2±1.4 (x10-3 mm2), but cimetidine (5.5±1.9, x10-3 mm2) did not. Similarly, the ratio of intimal area to medial area in the diphenhydramine-treated group but not in the cimetidine-treated group was significantly reduced (83%). In the in vitro study, cimetidine inhibited neither proliferation nor migration of mouse vascular smooth muscle cells stimulated by platelet-derived growth factor (PDGF). In contrast, diphenhydramine significantly (P<0.05) inhibited proliferation in a dose-dependent manner, but did not inhibit migration. These results suggest that diphenhydramine, a histamine H1 receptor antagonist, reduced the formation of intimal hyperplasia, at least in part due to inhibition of cell proliferation. However, cimetidine, a histamine H2 receptor antagonist, was ineffective. Histamine may play a key role in intimal thickening, in part via histamine H1 receptors in this model. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)53-59
Number of pages7
JournalEuropean Journal of Pharmacology
Issue number1
Publication statusPublished - 27-11-1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology


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