Biochemical and physiological effects of compound 48/80 on canine trachea in vivo.
We studied changes in tracheal histamine content and tracheal muscle tension after degranulation of tracheal mast cells by compound 48/80 in 32 anesthetized dogs. In four dogs compound 48/80 caused an increase in tracheal tension [13 +/- 5 (SD) g/cm], while femoral arterial blood pressure decreased only 14 +/- 11%. Tracheal tissue histamine decreased 17 +/- 6% in five dogs receiving intra-arterial compound 48/80 (5 X 10(-3) to 10(-1) mg/kg). Chlorpheniramine, an H1-antagonist, selectively inhibited tracheal contraction to compound 48/80 and histamine. Cimetidine, an H2-antagonist, did not alter the response to intra-arterial histamine. In 11 dogs, the doses of both intra-arterial histamine and acetylcholine required to produce a threshold increase in tracheal tension of 8 g/cm were compared. Threshold doses for acetylcholine varied 10-fold, compared with 100-fold variation for histamine among these dogs. There was a significant correlation between increased tracheal tension produced by compound 48/80 and histamine (r = 0.62). We conclude that compound 48/80 causes a variable increase in tracheal tension in vivo because of marked variability in the H1-receptor response of tracheal smooth muscle to histamine and because of variability in the release of mediator from respiratory mast cells by compound 48/80.
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001696:Biomechanical Phenomena; D002744:Chlorpheniramine / Q000494:pharmacology; D004285:Dogs / Q000502:physiology*; D005260:Female; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D007269:Injections, Intra-Arterial; D008297:Male; D011968:Receptors, Histamine / Q000187:drug effects; D014132:Trachea / Q000187:drug effects*; D003189:p-Methoxy-N-methylphenethylamine / Q000008:administration & dosage / Q000494:pharmacology*
D011968:Receptors, Histamine; D002744:Chlorpheniramine; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine; D000109:Acetylcholine