Histamine H₃ and H₄ Receptor Ligands Modify Vascular Histamine Levels in Normal and Arthritic Large Blood Vessels In Vivo

Growing evidence associates histamine with arthritis, but its implication in shaping vascular function in chronic inflammation remains largely elusive. This study explored the involvement of vascular histamine in the extra-articular responses in peripheral large blood vessels using a rat model of adjuvant-induced arthritis. Histamine levels were increased in the abdominal aorta and the inferior vena cava of arthritic animals. Contrary to the H₁ receptor antagonist dimetindene, histamine induction was observed following administration of the H₃ and H₄ receptor ligands GSK334429 and JNJ7777120, respectively. In arthritis, prophylactic treatment with GSK334429 partially attenuated the clinical signs and restored basal histamine levels only in the abdominal aorta. This study is the first to implicate the H₃ and H₄ receptors in a concerted constitutive regulation of basal vascular histamine in the rat large blood vessels and to identify the H₃ receptor as a component that may influence arterial histamine during the onset of arthritis.