H1- and H2-receptor characterization in the tracheal circulation of sheep.
1. The effects of histamine, the specific H1-agonist SKF 71481-A2 and the H2-agonist dimaprit were examined on tracheal vascular resistance in sheep anaesthetized with pentobarbitone. Tracheal vascular resistance was determined by perfusing the cranial tracheal arteries at constant flows and measuring inflow pressures. Changes in tracheal smooth muscle tone were also measured. 2. Histamine and SKF 71481-A2 contracted the tracheal smooth muscle and this effect was blocked by the H1-antagonist mepyramine. Stimulation of H2-receptors with dimaprit had no effect on tracheal smooth muscle tone. 3. Histamine had a complex action on the tracheal vasculature producing either a triphasic change (early dilatation then constriction followed by late dilatation) or just a constriction. SKF 71481-A2 always produced a biphasic change in vascular resistance (dilatation followed by constriction). Dimaprit dilated the tracheal vasculature. 4. The late dilatation produced by histamine in some sheep was blocked by bilateral cervical vagotomy but the mechanism for this effect is not known. No other responses to histamine, SKF 71481-A2 or dimaprit were affected by vagotomy. 5. The vasoconstriction produced by histamine and SKF 71481-A2 was antagonized by mepyramine indicating a H1-receptor-mediated effect. Cimetidine had no effect on the vasoconstriction to histamine suggesting a lack of involvement of H2-receptors. 6. The vasodilatation produced by histamine and SKF 71481-A2 was also antagonized by mepyramine, again suggesting a H1-receptor-mediated action. Cimetidine had no effect on the vasodilator response to histamine indicating no involvement of H2-receptors in this response. 7. The dilator effect of dimaprit was antagonized by cimetidine suggesting this effect was mediated by H2-receptors. 8. We conclude that H1-receptors in the various parts of the sheep tracheal vasculature can cause increases and decreases in total tracheal vascular resistance; that H2-receptors decrease resistance; and that the tracheal smooth muscle contracts on activation of H1-receptors but has no response to H2-agonists.
Webber
S E
SE
Department of Physiology, St George's Hospital Medical School, London.
Salonen
R O
RO
Widdicombe
J G
JG
D000818:Animals; D017259:Dimaprit; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D011970:Receptors, Histamine H2 / Q000378:metabolism* / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D013890:Thiourea / Q000494:pharmacology; D014132:Trachea / Q000098:blood supply / Q000378:metabolism*; D014628:Vagotomy; D014655:Vascular Resistance / Q000187:drug effects
D006635:Histamine H2 Antagonists; D011970:Receptors, Histamine H2; D006632:Histamine; D013890:Thiourea; D017259:Dimaprit