Alpha 2-adrenoceptor activation inhibits noradrenaline release in human and rabbit isolated renal arteries.
The aim of the present study was to investigate alpha 2-adrenoceptor modulation of noradrenaline release in superfused strips of human and rabbit renal arteries. The arteries were field-stimulated after incubation with [3H]noradrenaline. The stimulation-induced outflow of radioactivity was taken as an index of noradrenaline release. At a high stimulation frequency (4 Hz), the alpha 2-adrenoceptor agonist clonidine (0.1 mumol/l) failed to inhibit stimulation-induced outflow of radioactivity in human and rabbit renal arteries whereas the alpha 2-adrenoceptor agonist UK 14304 (0.1 mumol/l) did inhibit stimulation-induced outflow. The inhibitory effect of UK 14304 in human renal arteries was blocked by the alpha 2-adrenoceptor blocking drug rauwolscine (1 mumol/l). At a lower stimulation frequency (2 Hz), both clonidine and UK 14304 inhibited stimulation-induced outflow of radioactivity from rabbit renal arteries; both effects were blocked by rauwolscine. Rauwolscine by itself enhanced stimulation-induced outflow of radioactivity in both preparations. The results suggest that activation of prejunctional alpha 2-adrenoceptors in human and rabbit renal arteries inhibits noradrenaline release. Neuronally released noradrenaline exerts inhibitory feed-back modulation of its own release through activation of prejunctional alpha 2-adrenoceptors. At a higher stimulation frequency most of the prejunctional alpha 2-adrenoceptors are already occupied by endogenous noradrenaline and clonidine fails to inhibit noradrenaline release since it seems to act as a partial agonist at these prejunctional alpha 2-adrenoceptors.
Medizinische Universitätsklinik Freiburg, Innere Medizin IV, F.R.G.
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D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000068438:Brimonidine Tartrate; D003000:Clonidine / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000294:innervation; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D013779:Tetrodotoxin; D000068438:Brimonidine Tartrate; D003000:Clonidine; D009638:Norepinephrine