6533b853fe1ef96bd12ac309

RESEARCH PRODUCT

Role of endothelium in the responses to noradrenaline in normal and sensitized guinea-pig aorta

subject

description

1. The pharmacological reactivity of sensitized blood vessels has been less studied than that of the airways. Aorta rings were obtained from normal (non-sensitized) and actively sensitized guinea-pigs, and prepared for isometric recording of tension changes. 2. Noradrenaline (10 nM-0.1 mM), histamine (0.1 microM-0.1 mM) and KCl (10-100 mM) produced concentration-related contractions of normal tissues. Removal of endothelium resulted in a marked leftward and upward shift of the concentration-response curve for noradrenaline but it did not alter histamine- or KCl-induced responses. Pretreatment with L-NG-nitroarginine (L-NOARG, 30 microM), haemoglobin (5 microM) or ibuprofen (10 microM) enhanced noradrenaline-induced responses without affecting those to histamine or KCl. 3. Removal of endothelium or pretreatment with L-NOARG or ibuprofen did not alter agonist-induced responses in sensitized tissues. Acetylcholine (1 microM)-induced relaxation of the contraction produced by noradrenaline (1 microM) in intact rings was diminished in sensitized compared to normal tissues. 4. Neuronal uptake and release of [3H]-noradrenaline did not differ in normal and sensitized tissues. 5. Loss of the modulatory role of endothelium and other mechanisms may be involved in the hyperreactivity of sensitized guinea-pig aorta.