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Reversal of vascular tachyphylaxis to catecholamines and histamine in the feline lung.
- Source :
-
The American review of respiratory disease [Am Rev Respir Dis] 1988 Jun; Vol. 137 (6), pp. 1336-42. - Publication Year :
- 1988
-
Abstract
- The pulmonary vascular responses to histamine, epinephrine, and norepinephrine demonstrate tachyphylaxis following repetitive exposure in the isolated blood-perfused cat lung. 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. In addition, histamine demonstrated a significant increase in ED50 from DR I to IV, which suggested a loss of sensitivity. The loss of vasoconstrictor activity to histamine and the catecholamines was restored by the administration of propranolol prior to DR V. In contrast, cimetidine did not restore the initial vasopressor activity of histamine. The loss of reactivity to histamine was not secondary to changes in circulating catecholamine levels, because the plasma catecholamine levels before DR I and immediately following DR V in a subset of animals (n = 5) were within the reported normal range for this species.(ABSTRACT TRUNCATED AT 250 WORDS)
- Subjects :
- Animals
Blood Vessels drug effects
Cats
Cimetidine pharmacology
Dose-Response Relationship, Drug
In Vitro Techniques
Indomethacin pharmacology
Lung drug effects
Lung physiology
Male
Propranolol pharmacology
Receptors, Adrenergic, beta drug effects
Receptors, Histamine H1 drug effects
Vascular Resistance drug effects
Epinephrine pharmacology
Histamine pharmacology
Norepinephrine pharmacology
Pulmonary Circulation drug effects
Tachyphylaxis
Subjects
Details
- Language :
- English
- ISSN :
- 0003-0805
- Volume :
- 137
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The American review of respiratory disease
- Publication Type :
- Academic Journal
- Accession number :
- 2849331
- Full Text :
- https://doi.org/10.1164/ajrccm/137.6.1336