Histamine H1 receptors mediate vasodilation in guinea-pig ileum resistance vessels: characterization with computer-assisted videomicroscopy and new selective agonists

Histamine receptors on guinea-pig ileum submucosal arterioles (outside diameter 40-80 microns) were studied in vitro using a computer-assisted videomicroscopy system (Diamtrak). Histamine Receptor agonists investigated in this study were histamine, the H1 receptor-selective compound, 2-[2-(3-fluorophenyl)-4-imidazolyl]ethanamine (VZ 20), the H2 receptor-selective compounds, dimaprit, impromidine, (+/-)-N1-[3-(4-fluorophenyl)-3-(pyridin-2-yl)propyl]- N2-[3-(1H-imidazol-4-yl)propyl]guanidine (arpromidine) and (+/-)-N1-[3-(3,4-difluorophenyl)-3-(pyridin-2-yl)propyl]- N2-[3-(1H-imidazol-4-yl)propyl]guanidine (BU-E-75), as well as the H3 receptor-selective drug, (R)-alpha-methylhistamine ((R)-alpha-MeHA). Applied to vessels at resting tone, the agonists (1 nM-300 microM) did not change arteriolar diameter. Vessels preconstricted by 10 microM noradrenaline showed similar concentration-dependent vasodilations with histamine and VZ 20 (pD2 = 5.38 and 5.36, respectively). This histamine-induced vasodilation was not affected by tetrodotoxin (0.5 microM) or indomethacin (1 microM), but was completely abolished in the presence of 1 microM of the H1 receptor antagonist, mepyramine. Calculation of the antagonist affinity of mepyramine for the histamine receptors in submucosal arterioles yielded a pA2 of 9.46. In contrast to histamine and VZ 20, the H2 receptor agonist, dimaprit, and the H3 receptor agonist, (R)-alpha-MeHA, were ineffective at preconstricted arterioles. The guanidine-type H2 receptor agonists, impromidine, apromidine and BU-E-75, produced vasodilation at noradrenaline-preconstricted arterioles (-log EC50 = 4.47, 5.30 and 5.39, respectively) but, in contrast to histamine, were ineffective at arterioles preconstricted by U-46619 (300 nM).(ABSTRACT TRUNCATED AT 250 WORDS)