Biochemical evidence that brainstem adrenaline-containing neurons are activated during clonidine withdrawal in the spontaneously hypertensive rat
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We have investigated the effects of prolonged treatment with clonidine (delivered intravenously via osmotic minipumps, 0.1 mg/kg/day for 7 or 10 days) and of withdrawal of such treatment on brainstem noradrenaline and adrenaline metabolism in the adult spontaneously hypertensive rat (SHR). After a seven day treatment with clonidine, noradrenaline and adrenaline turnovers were unchanged both in the A2-C2 and A1-C1 regions. During withdrawal, the noradrenaline turnover was also unchanged in these regions. However, the adrenaline turnover was significantly increased 16 h after withdrawal (p < 0.01) in the A2-C2 region and 16 h (p < 0.01) and 40 h (p < 0.05) after withdrawal in the A1-C1 region. These results show that noradrenaline metabolism is unchanged both during clonidine treatment and during its withdrawal in the brainstem catecholaminergic regions analyzed. In contrast, the increases in adrenaline turnover found in the A2-C2 and A1-C1 regions suggest that the adrenergic neurons of the brainstem could be activated during clonidine withdrawal. As the adrenergic CI neurons are a key element of the sympathetic vasopressor system, the increase in adrenaline turnover observed during withdrawal could be at the origin of the sympathetic hyperactivity found after cessation of prolonged treatment with clonidine.
Key-wordsAdrenaline Clonidine Noradrenaline Turnover Withdrawal
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- Fuxe K, Bolme P, Agnati LF, Jonsson G, Andersson K, Köhler C, Hökfelt T (1980) On the role of central adrenaline neurons in central cardiovascular regulation. In: Fuxe K, Goldstein M, Hökfelt B, Hökfelt T (eds) Central adrenaline neurons. Basic aspects and their role in cardiovascular functions. Pergamon Press, Oxford, pp 161–182CrossRefGoogle Scholar
- Fuxe K, Agnati LF, Ganten D, Goldstein M, Yukimura T, Jonsson G, Bolme P, Hökfelt T, Andersson K, Härfstrand A, Unger T, Rascher W (1981) The role of noradrenaline and adrenaline neuron systems and substance P in the control of central cardiovascular functions. In: Buckley JP, Ferrario CM (eds) Central nervous system mechanism in hypertension. Raven Press, New York, pp 89–113Google Scholar
- Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
- Reis DJ (1986) The C1 area of rostral ventrolateral medulla: role in tonic and reflex regulation of arterial pressure. In: Magro A, Oswald W, Reis DJ, Van Houtte P (eds) Central and peripheral mechanisms of cardiovascular regulation. Plenum Publishing Corporation, New York, pp 487–502CrossRefGoogle Scholar
- Scatton B, Pelayo F, Dubocovich ML, Langer SZ, Bartholini G (1979) Effects of clonidine on the cerebral adrenaline turnover and the adrenaline release in nucleus tractus solitarii of the rat. In: Langer SZ, Starke K, Dubocovich ML (eds) Presynaptic receptors. Pergamon Press, Oxford, pp 231–236Google Scholar
- Scatton B, Bartholini G (1980) Effects of antihypertensives and other drugs on central adrenaline utilisation. In: Fuxe K, Goldstein M, Hökfelt B, Hökfelt T (eds) Central adrenaline neurons. Basic aspects and their role in cardiovascular functions. Pergamon Press, Oxford, pp 183–197CrossRefGoogle Scholar