Presynaptic imidazoline receptors mediate inhibition of noradrenaline release from sympathetic nerves in rat blood vessels.
In rat vena cava and aorta preincubated with [3H]noradrenaline the involvement of imidazoline receptors in modulation of [3H]noradrenaline release from sympathetic nerves was investigated. In the vena cava, the guanidine 1,3-di(2-tolyl)guanidine (DTG) inhibited the electrically evoked [3H]noradrenaline release; the inhibitory effect was more pronounced in the presence than in the absence of the alpha 2-adrenoceptor antagonist rauwolscine. The concentration-response curves of BDF 6143 [4-chloro-2-(2-imidazolin-2-ylamino)-isoindoline], and idazoxan for their facilitatory effect on electrically evoked [3H]noradrenaline release was bell-shaped; in the presence of rauwolscine, BDF 6143 inhibited the evoked [3H]noradrenaline release, whereas idazoxan did not. After blockade of alpha 2-autoreceptors by rauwolscine, the electrically evoked [3H]noradrenaline release from vena cava was inhibited not only by DTG and BDF 6143 but also by aganodine, clonidine and cirazoline; the rank order of potency of most of the drugs was similar to that found at the presynaptic imidazoline receptors in the rabbit aorta and pulmonary artery as well as in human atrial appendages. In the presence of rauwolscine, clonidine-induced inhibition of electrically evoked [3H]noradrenaline release was counteracted by 1 microM of the selective CB1 receptor antagonist SR141716A (N-[piperidin-1-yl]-5-[4-chlorophenyl]-1-[2,4-dichlorophenyl] -4-methyl-1H-pyrazole-3-carboxamide). In the aorta, BDF 6143 and cirazoline did not modify [3H]noradrenaline release in the absence of alpha 2-adrenoceptor blockade; in the presence of rauwolscine, the electrically evoked [3H]noradrenaline release from aorta was inhibited by BDF 6143, cirazoline, aganodine and clonidine with a rank order of potency similar to that in the vena cava. SR141716A 1 microM antagonized the inhibitory effect of BDF 6143 and clonidine (in the presence of rauwolscine). In conclusion, noradrenaline release in rat vena cava and aorta is inhibited via presynaptic imidazoline receptors which appear to be related to those previously characterized in rabbit and human cardiovascular tissue.
Molderings
G J
GJ
Institut für Pharmakologie und Toxikologie, Rheinischen Friedrich-Wilhelms-Universität Bonn, Germany.
Göthert
M
M
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D054755:Imidazoline Receptors; D054833:Isoindoles; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium / Q000378:metabolism; D014684:Venae Cavae / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*
D007093:Imidazoles; D054755:Imidazoline Receptors; D054833:Isoindoles; D011955:Receptors, Drug; D017661:Receptors, Presynaptic; D014316:Tritium; C036966:4-chloro-2-(2-imidazolin-2-ylamino)isoindoline; D009638:Norepinephrine