Peripheral presynaptic and central effects of clonidine, yohimbine and rauwolscine on the sympathetic nervous system in rabbits.
The function of presynaptic alpha 2-autoreceptors at postganglionic sympathetic neurones under conditions of normal, ongoing sympathetic impulse traffic was studied in anaesthetized rabbits (alfadolone + alfaxalone). Clonidine was used as an alpha 2-adrenoceptor agonist, and yohimbine and rauwolscine were used as antagonists. Mean arterial pressure, postganglionic renal sympathetic firing rate, arterial plasma noradrenaline concentration and heart rate were measured before (basal values) and at the end of 3-min infusions of sodium nitroprusside and phenylephrine, which were given to modulate efferent activity in the sympathetic nervous system through the baroreflex. The nitroprusside- and phenylephrine-induced changes of mean arterial pressure produced the expected changes in sympathetic nerve activity, plasma noradrenaline and heart rate. Clonidine (5 micrograms kg-1 + 0.5 micrograms kg-1 min-1) reduced the basal mean arterial pressure, sympathetic nerve activity and heart rate. It also reduced the nitroprusside-induced increase in the plasma noradrenaline level without changing the nitroprusside-induced increase in sympathetic firing. These results, as well as the mean arterial pressure-sympathetic nerve activity and the sympathetic nerve activity-plasma noradrenaline function curves indicate that clonidine inhibited both sympathetic tone centrally and the average release of noradrenaline per action potential peripherally. Yohimbine (1 mg kg-1 + 0.1 mg kg-1 h-1) and rauwolscine (0.5 mg kg-1 + 0.1 mg kg-1 h-1) increased the basal plasma noradrenaline level without any increase of renal sympathetic nerve activity. They also enhanced the nitroprusside-induced increase in plasma noradrenaline without any enhancement of the nitroprusside-induced increase in sympathetic firing. The hypotensive response to nitroprusside was attenuated, whereas the heart rate response was augmented. These results, as well as the mean arterial pressure-sympathetic nerve activity and the sympathetic nerve activity-plasma noradrenaline function curves indicate that the main effect of yohimbine and rauwolscine was to increase the average release of noradrenaline per action potential. The simultaneous measurement of postganglionic sympathetic nerve activity and the arterial plasma noradrenaline concentration proved suitable to differentiate central (or ganglionic; this distinction was not possible) effects of alpha 2-adrenoceptor ligands from peripheral presynaptic effects. The results show that endogenous presynaptic, alpha 2-adrenergic autoinhibition of noradrenaline release from postganglionic sympathetic neurones operates physiologically in anaesthetized rabbits with ongoing, uninterrupted sympathetic nerve activity. The results also indicate that blockade of alpha 2-autoreceptors enhances the sympathetic reflex compensatory response to a hypotensive stimulus.
Szabo
B
B
Pharmakologisches Institut der Universität, Freiburg, Federal Republic of Germany.
Hedler
L
L
Starke
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D010525:Peripheral Nerves / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology*
D009599:Nitroprusside; D010656:Phenylephrine; D015016:Yohimbine; D003000:Clonidine; D009638:Norepinephrine