Concentrations of noradrenaline at neuronal uptake sites during sympathetic nervous inhibition and activation in rabbits.
Concentrations of noradrenaline at peripheral neuronal uptake sites were examined during sustained changes in sympathetic nervous activity produced by intracisternal infusion of yohimbine or clonidine in conscious rabbits. The gradient between concentrations of noradrenaline in plasma and at neuronal uptake sites was estimated by comparing the formation of the intraneuronal metabolite of noradrenaline, dihydroxyphenylglycol (DHPG), from intravenously infused and endogenously released noradrenaline. At resting levels of sympathetic activity the noradrenaline concentration at neuronal uptake sites (4.2 +/- 0.5 nmol/l) was 3.4-fold greater than the concentration in arterial plasma (1.3 +/- 0.1 nmol/l). Noradrenaline at neuronal uptake sites increased to 9.4 +/- 1.3 nmol/l after yohimbine and decreased to 2.4 +/- 0.1 nmol/l after clonidine. The noradrenaline concentration gradient was not altered by intracisternal infusion of yohimbine or clonidine. Thus, a positive linear relationship (r = 0.97) was observed between concentrations of noradrenaline at neuronal uptake sites and in plasma. The gradient was positively related to the efficiency of noradrenaline reuptake (r = 0.81). The results show that arterial plasma concentrations of noradrenaline are considerably less than concentrations close to sites of release, but accurately reflect changes in amounts of noradrenaline at release sites during sustained changes in sympathetic activity. The gradient in noradrenaline concentrations between neuronal uptake sites and plasma is largely dependent on the efficiency of neuronal reuptake. Since the gradient is not altered by sympathetic nervous inhibition or activation, the proportion of noradrenaline removed by neuronal and extraneuronal uptake does not appear to be altered by moderate changes in transmitter release.
Eisenhofer
G
G
Clinical Neuroscience Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892.
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D009599:Nitroprusside; D015016:Yohimbine; D008734:Methoxyhydroxyphenylglycol; D003000:Clonidine; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine