Acetylcholine-induced relaxation of the rabbit aorta is preload-independent but markedly dependent upon the degree of excitatory agonist-induced tone.
1. The aim of the present study was to investigate the relationship between endothelium-dependent relaxation evoked by acetylcholine, tissue preload and the degree of noradrenaline-induced tone in the isolated rabbit aorta. 2. In the aorta preload-response curves were bell-shaped with increasing preload augmenting responses to noradrenaline up to a certain point (optimal value) and then declining. Removal of the endothelium significantly increased responses to low concentrations of noradrenaline (less than 0.1 microM) but did not significantly affect the maximum response of the aorta to this amine or the preload-response curves generated at several concentrations of noradrenaline. 3. The optimal preload value was around 10 g for the aorta and changes in preload did not influence the sensitivity of the tissue to noradrenaline as assessed by pEC50 values to this agonist. 4. Acetylcholine (0.01-10 microM) evoked endothelium-dependent relaxations which in absolute terms increased as the tissue preload was increased. This relationship was much less evident when acetylcholine responses were measured in terms of the percentage inhibition of the respective noradrenaline contraction, when little or no change in the acetylcholine responses was noted. 5. When acetylcholine relaxations were expressed in terms of a percentage of the maximum noradrenaline-induced response evoked at each preload setting, the results confirmed that preload changes had little or no influence upon acetylcholine responses. 6. In contrast, tissue sensitivity to, and the extent of acetylcholine-induced relaxation, were markedly affected by the level of excitatory agonist-induced tone. As noradrenaline-induced tone increased, maximum responses and pIC50 values to acetylcholine were reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
John
G W
GW
Department of Pharmacology, RL-CERM, Riom, France.
Degeorge
F
F
Massingham
R
R
D000109:Acetylcholine / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D005576:Colforsin; D000109:Acetylcholine; C014282:cirazoline; D009638:Norepinephrine