title: Protective effects of histamine on Gq-mediated relaxation in regenerated endothelium.
abstract: In the porcine coronary artery, regenerated endothelium is dysfunctional as regards the responses to endothelium-dependent agonists. The current study aimed to determine the possible involvement of histamine in such dysfunction. Pigs were treated chronically with pyrilamine (H1 receptor inhibitor, 2 mg·kg(-1)·day(-1)) with part of their coronary endothelium and allowed to regenerate for 28 days after balloon denudation. The results showed a reduction in relaxation to bradykinin (Gq protein dependent) only in the pyrilamine-treated group (area under the curve, 269.7 ± 13.4 vs. 142.0 ± 31.0, native endothelium vs. regenerated endothelium) but not in the control group (253.0 ± 22.1 vs. 231.9 ± 29.5, native endothelium vs. regenerated endothelium). The differences in the relaxation to serotonin (Gi protein dependent) between native and regenerated endothelium were not affected by the pyrilamine treatment (control group, 106.3 ± 17.0 vs. 55.61 ± 12.7; and pyrilamine group, 106.0 ± 8.20 vs. 49.30 ± 6.31, native endothelium vs. regenerated endothelium). These findings indicate that during regeneration of the endothelium, the activation of H1 receptors by endogenous histamine may be required to maintain the endothelium-dependent Gq protein-mediated relaxation to bradykinin, suggesting a beneficial role of the monoamine in the process of endothelial regeneration.
authors.affiliation: Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China;
authors.forename: Calvin K
authors.initials: CK
authors.lastname: Chan
authors.forename: Song Yan
authors.initials: SY
authors.lastname: Liao
authors.forename: Yue Lin
authors.initials: YL
authors.lastname: Zhang
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.forename: Hung Fat
authors.initials: HF
authors.lastname: Tse
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vanhoutte
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D003331:Coronary Vessels / Q000293:injuries; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D009126:Muscle Relaxation / Q000187:drug effects*; D011738:Pyrilamine / Q000494:pharmacology* / Q000627:therapeutic use; D012038:Regeneration; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D006634:Histamine H1 Antagonists; D014665:Vasodilator Agents; D012701:Serotonin; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D011738:Pyrilamine; D001920:Bradykinin
keywords: bradykinin; endothelial cells; histamine