HI-and Hz-histamine receptor-mediated vasodilation varies with aging in humans
Introductim: Aging is associated with alterations in the responses to several important vasoactive drugs. We have investigated histamine-mediated venodilation across the adult age range using the human hand vein compliance technique. Histamine produces dilation in human veins by activating both H,-and Hareceptors. Metboa%: Full dose-response curves to histamine were consmtcted in 16 healthy volunteers (mean age, 47 + 20 years; age range, 21 to 80 years) by infusing histamine (2 to 136 ng/min) into dorsal hand veins preconstricted with the a-adrenergic selective agonist phenylephrine. Rtmlts: Histamine was an efficacious venodilator across the age range; the average maximal response (E,,) was 122 + 45% and the geometric mean ED,, (the dose producing half-maximal response) was 16.6 ng/min for all subjects. Dose-response curves to histamine were repeated after infusion of the Haselective antagonist cimetidine at a dose suflicient to completely block the Ha-mediated response (49 p&I mm). Cimetidine did not inhibit the E,, in the elderly as much as it did in the young subjects. The E to histamine in the presence of cimetidine plotted against age showed a significant relationship (,"z 0.62,~ = 0.02). Cunc1u.s~: These results suggest that, although the overall histamine-induced venodilation is conserved in aging, there is a loss of the signal transduction pathway activated by way of Ha-receptors but no loss in function of HI-receptors. Consequently, these results suggest differential changes in function of H,versus Ha-histamine receptors with aging. Because HI-receptors are coupled to endothelial-derived relaxing factor release and because Ha-receptors activate cyclic adenosine monophosphate in smooth muscle, the results are compatible with hypothesis that there are specific changes in these signal transduction pathways with aging. (CLIN PHARMA COL 'Iha 1995;58:73-80.