Summary
Liquid chromatographic fractionation and detection of exogenous radiolabelled and endogenous catechols was used to examine simultaneously the plasma kinetics of noradrenaline and adrenaline in the conscious rabbit. Plasma clearances and release of noradrenaline and adrenaline into plasma were compared before and during nitroprusside-induced hypotension and 2-deoxyglucose-induced glucopenia, stimuli purported to differentially affect catecholamine release from sympathetic neurons and the adrenal medulla. Plasma concentrations of dihydroxyphenylglycol (DHPG) were also measured to assess presynaptic sympathetic function.
Plasma clearances of adrenaline correlated with, but were significantly less than those of noradrenaline. Plasma clearances of both catecholamines showed significant decreases during nitroprusside-induced hypotension and 2-deoxyglucose-induced glucopenia. Glucopenia and hypotension increased the release into plasma of noradrenaline and adrenaline, but the adrenaline response relative to the noradrenaline response was greater during glucopenia than during hypotension. Plasma DHPG concentrations increased during glucopenia and hypotension, consistent with increased neuronal reuptake of noradrenaline and therefore a neuronal source — as opposed to an adrenal source — of most of the noradrenaline appearing in plasma during the stimuli. The increase in plasma DHPG relative to that of noradrenaline was greater after 2-deoxyglucose than after nitroprusside suggesting that the presynaptic handling of noradrenaline during glucopenia was different from that during hypotension or that the two stimuli released DHPG from regionally distinct sources.
Similar content being viewed by others
References
Bradley T, Hjemdahl P (1986) Renal overflow of noradrenaline and dopamine to plasma during hindquarter compression and thoracic inferior vena cava obstruction in the dog. Acta Physiol Scand 127:305–312
Brown J (1962) Effects of 2-deoxyglucose on carbohydrate metabolism: review of the literature and studies in the rat. Metabolism 11:1098–1112
Brown MJ (1984) Simultaneous assay of noradrenaline and its deaminated metabolite, dihydroxyphenylglycol, in plasma: a simplified approach to the exclusion of phaeochromocytoma in patients with borderline elevation of plasma noradrenaline concentration. Eur J Clin Invest 14:67–72
Christensen NJ, Galbo H, Gjerris A, Henriksen JH, Hilsted J, Kjaer M, Ring-Larsen H (1984) Whole body and regional clearances of noradrenaline and adrenaline in man. Acta Physiol Scand [Suppl] 527:17–20
Eisenhofer G, Goldstein DS, Stull R, Ropchak TG, Keiser HR, Kopin IJ (1987) Dihydroxyphenylglycol and dihydroxymandelic acid during intravenous infusions of noradrenaline. Clin Sci 73:123–127
Eisenhofer G, Goldstein DS, Ropchak TG, Nguyen HQ, Keiser HR, Kopin IJ (1988) Source and physiological significance of plasma 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol. J Auton Nerv Syst 24:1–14
Ester M, Lambert G (1988) Tritiated dihydroxyphenylethylene glycol in plasma? Clin Sci 75:109–111
Esler M, Jackman G, Bobik A, Kelleher D, Jennings G, Leonard P, Skews H, Kerner P (1979) Determination of norepinephrine apparent release rate and clearance in humans. Life Sci 25: 1461–1470
Ester M, Jennings G, Korner P, Willet I, Dudley F, Hasking G, Anderson W, Lambert G (1988) Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover. Hypertension 11:3–20
Folkow B, Di Bona GF, Hjemdahl P, Toren PH, Wallin BG (1983) Measurement of plasma norepinephrine concentrations in human primary hypertension: a word of caution on their applicability for assessing neurogenic contributions. Hypertension 5:399–403
Goldstein DS, Horowitz D, Keiser HR, Polinsky RJ (1983) Plasma 1-[3H]norepinephrine, d-[14C]norepinephrine and d,l-[3H]isoproterenol kinetics in essential hypertension. J Clin Invest 72:1748–1758
Goldstein DS, Eisenhofer G, Sax F, Keiser HR, Kopin IJ (1987) Plasma norepinephrine pharmacokinetics during mental challenge. Psychosom Med 49:591–605
Goldstein DS, Brush JE, Eisenhofer G, Stull R, Esler M (1988a) In vivo measurement of neuronal uptake of norepinephrine in the human heart. Circulation 78:41–48
Goldstein DS, Eisenhofer G, Stull R, Folio CJ, Keiser HR, Kopin IJ (1988b) Plasma dihydroxyphenylglycol and the intraneuronal disposition of norepinephrine in humans. J Clin Invest 81:213–220
Hagbarth K-E, Vallbo AB (1968) Pulse and respiratory grouping of sympathetic impulses in human muscle nerves. Acta Physiol Scand 74:96–108
Halbrügge T, Ungell AL, Wölfel R, Graefe K-H (1988) Total body, systemic and pulmonary clearance and fractional extraction of unlabelled and differently 3H-labelled noradrenaline in the anaesthetized rabbit. Naunyn-Schmiedeberg's Arch Pharmacol 338:361–367
Hasking GJ, Ester MD, Jennings GL, Burton D, Johns JA, Korner PI (1986) Norepinephrine spillover to plasma in patients with congestive heart failure; evidence of increased overall and cardiorenal sympathetic nervous activity. Circulation 73:615–621
Havel PJ, Veith RC, Dunning BE, Taborsky GJ (1988) Pancreatic noradrenergic nerves are activated by neuroglucopenia but not by hypotension or hypoxia in the dog. Evidence for stress-specific and regionally selective activation of the sympathetic nervous system. J Clin Invest 82:1538–1545
Henriksen JH, Christensen NJ, Ring-Larsen H (1986) Pulmonary extraction of circulating noradrenaline in man. Ear J Clin Invest 16:423–427
Howes LG, MacGilchrist A, Hawksby C, Sumner D, Reid JL (1986) An improved approach for the determination of plasma [3H]noradrenaline kinetics using high performance liquid chromatography. Clin Sci 71:211–215
Iversen LL (1965) The uptake of adrenaline by the rat isolated heart. Br J Pharmacol 24:387–394
Keeton TK, Biediger AM (1988) The measurement of norepinephrine clearance and apparent release rate in the conscious spontaneously hypertensive rat. Naunyn-Schmiedeberg's Arch Pharmacol 339:350–360
Ludwig J, Gerhardt T, Halbrügge T, Walter J, Graefe K-H (1988) Plasma concentrations of noradrenaline and 3,4-dihydroxyphenylethyleneglycol under conditions of enhanced sympathetic activity. Eur J Clin Pharmacol 35:261–267
Majewski H, Hedler L, Starke K (1983a) Modulation of noradrenaline release in the conscious rabbit through α-adrenoceptors. Eur J Pharmacol 93:255–264
Majewski H, Rump LC, Hedler L, Starke K (1983b) Effects of α1- and α2-adrenoceptor blocking drugs on noradrenaline release rate in anaesthetized rabbits. J Cardiovasc Pharmacol 5:703–711
McCarty R (1986) Age-related alterations in sympatho-adrenal medullary responses to stress. Gerontology 32:172–183
Medvedev OS, Delle M, Thoren P (1988) 2-Deoxyglucose-induced central glycopenia differentially influences renal and adrenal nerve activity in awake SHR rats. Clin Exp Hypertens [A] 10:375–381
Morrow LA, Linares OA, Hill TJ, Sanfield JA, Supiano MA, Rosen SG, Halter JB (1987) Age differences in the plasma clearance mechanisms for epinephrine and norepinephrine in humans. J Clin Endocrinol Metab 65:508–511
Needleman P, Corr PB, Johnson EM (1985) Drugs used for the treatment of angina: organic nitrates, calcium channel blockers, and β-adrenergic antagonists. In: Goodman Gilman A, Goodman LS, Rall TW, Murad F (eds) The pharmacological basis of therapeutics. Macmillan, New York, pp 806–826
Niijima A (1975) The effect of 2-deoxy-D-glucose and D-glucose on the efferent discharge rate of sympathetic nerves. J Physiol (Lond) 251:231–243
Veith RC, Featherstone JA, Linares OA, Halter JB (1986) Age differences in plasma norepinephrine kinetics in humans. J Gerontol 41:319–325
Victor RG, Thoren P, Morgan DA, Mark AL (1989) Differential control of adrenal and renal sympathetic nerve activity during hemorrhagic hypotension in rats. Circ Res 64:686–694
Yamaguchi N, Brassard M, Briand R (1988) Contribution of adrenal norepinephrine output to increase aortic norepinepbrine during carotid sinus reflex activation in anesthetized dogs. Life Sci 42:1101–1108
Ziegler MG, Chernow B, Woodson LC, Coyle J, Cruess D, Lake R (1986) The effect of propranolol on catecholamine clearance. Clin Pharmacol Ther 40:116–119
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Medvedev, O.S., Esler, M.D., Angus, J.A. et al. Simultaneous determination of plasma noradrenaline and adrenaline kinetics. Naunyn-Schmiedeberg's Arch Pharmacol 341, 192–199 (1990). https://doi.org/10.1007/BF00169730
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00169730