Effects of histamine-receptor agonists on transvascular fluid and macromolecular efflux in the canine forelimb

Histamine increases transvascular fluid and protein efflux in the canine forelimb resulting in edema formation. To clarify the receptor mechanisms of histamine edema, we infused H1 and H2-receptor agonists into the forelimb perfused at constant flow while measuring skin lymph parameters or forelimb weight. The H1-receptor agonist 2(2-pyridyl) ethylamine [PEA] or the H2-receptor agonist 4-methyl histamine (8-40 micrograms/min) singly or in combination fails to increase lymph flow, protein concentration or protein transport. PEA in a dose of 80-400 micrograms/min increases lymph flow, protein concentration and protein transport. 4-Methyl histamine in a dose of 40-200 micrograms/min produces a small but significant decrease in lymph flow and protein transport subsequent to a fall in systemic pressure. 4-Methyl histamine at 40 and 80 micrograms/min produces a progressive and sustained increase in forelimb weight PEA at 40 micrograms/min produces a small increase in forelimb weight which quickly plateaus much like the response seen with acetylcholine (10 micrograms base/min). However, infusion of PEA at 80 micrograms/min progressively increases forelimb weight, similar to that seen with 4-methyl histamine or histamine (1.4 microgram base/min). These data indicate that either H1 or H2-receptor agonists can cause edema formation in the canine forelimb, and imply that histamine edema involves both H1 and H2-receptor interaction.