Reversal of vascular tachyphylaxis to catecholamines and histamine in the feline lung.

The pulmonary vascular responses to histamine, epinephrine, and norepinephrine demonstrate tachyphylaxis following repetitive exposure in the isolated blood-perfused cat lung (2). In the present study, we tested the hypothesis that this phenomenon was related to a change in the balance of antagonistic receptor activity. The protocol consisted of 5 consecutive dose-response maneuvers (DR I to V) to 1 amine in each animal separated by 1 h. Once the loss of the initial vasoconstrictor activity had occurred (DR I to IV), the animal was given a receptor blocking agent, either the beta blocker propranolol or the H2 blocker cimetidine, prior to a final dose-response maneuver (DR V). The dose-response relationships were analyzed in terms of 3 parameters: maximum response, slope, and ED50. All the experiments with norepinephrine (n = 6), epinephrine (n = 10), and histamine (n = 25) demonstrated a progressive loss of vasopressor activity as shown by reductions in the maximum response and slope between DR I to IV. I...