Evidence for a physiological role of presynaptic alpha-adrenoceptors: modulation of noradrenaline release in the pithed rabbit.
Rabbits were pithed and the preganglionic nerves at T 8 were stimulated continuously at a frequency of 3 Hz. 3H-noradrenaline was infused to reach a steady-state plasma level, from which the noradrenaline plasma clearance was calculated. The plasma level of endogenous noradrenaline was also determined and the rate of noradrenaline release into the plasma was then derived. The noradrenaline plasma clearance was decreased by guanethidine (7.5 mg/kg), desipramine (1 mg/kg), yohimbine (1 mg/kg) and rauwolscine (1 mg/kg). It was unaffected by corynanthine (1 mg/kg), prazosin (0.1 mg/kg), alpha-methylnoradrenaline (2 micrograms/kg per min) and clonidine (1 micrograms/kg per min). The electrical stimulation resulted in an increase in blood pressure without an increase in heart rate. Both adrenaline and noradrenaline were detected in the plasma. It is likely that the noradrenaline was of neuronal origin as guanethidine decreased its plasma level. The alpha 2-adrenoceptor-selective blocking drugs yohimbine and rauwolscine increased the noradrenaline release rate and only slightly decreased blood pressure. On the other hand, the alpha 1-adrenoceptor-selective blocking drugs corynanthine and prazosin had no effect on the noradrenaline release rate and decreased blood pressure more markedly. The alpha 2-adrenoceptor-selective agonists alpha-methylnoradrenaline and clonidine both decreased the noradrenaline release rate. This effect was blocked by yohimbine, and for the case of clonidine, not blocked by corynanthine. Plasma adrenaline levels were increased by yohimbine and rauwolscine, but not by corynanthine and prazosin. Clonidine reduced the plasma adrenaline level.(ABSTRACT TRUNCATED AT 250 WORDS)
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004558:Electric Stimulation; D004837:Epinephrine / Q000097:blood; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008771:Nordefrin / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013127:Spinal Nerves / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D003000:Clonidine; D008771:Nordefrin; D003891:Desipramine; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine; D006145:Guanethidine