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H 1 ‐ and H 2 ‐histamine receptor—mediated vasodilation varies with aging in humans
Author(s) -
Bedarida Gabriella,
Bushell Erin,
Blaschke Terrence F.,
Hoffman Brian B.
Publication year - 1995
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/0009-9236(95)90074-8
Subject(s) - histamine , cimetidine , phenylephrine , histamine h2 receptor , agonist , histamine h1 receptor , medicine , receptor , vasodilation , endocrinology , histamine receptor , antagonist , blood pressure
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 1 ‐ and H 2 ‐receptors. Methods Full dose‐response curves to histamine were constructed 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 α‐adrenergic selective agonist phenylephrine. Results Histamine was an efficacious venodilator across the age range; the average maximal response (E max ) was 122 ± 45% and the geometric mean ED 50 (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 H 2 ‐selective antagonist cimetidine at a dose sufficient to completely block the H 2 ‐mediated response (49 μg/min). Cimetidine did not inhibit the E max in the elderly as much as it did in the young subjects. The E max to histamine in the presence of cimetidine plotted against age showed a significant relationship ( r = 0.62, p = 0.02). Conclusions 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 H 2 ‐receptors but no loss in function of H 1 ‐receptors. Consequently, these results suggest differential changes in function of H 1 ‐versus H 2 ‐histamine receptors with aging. Because H 1 ‐receptors are coupled to endothelial‐derived relaxing factor release and because H 2 ‐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. Clinical Pharmacology & Therapeutics (1995) 58 , 73–80; doi: 10.1016/0009‐9236(95)90074‐8