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Long term β-adrenergic blockade reduces tyrosine hydroxylase and dopamine β-hydroxylase activities in sympathetic ganglia

Abstract

β-ADRENOCEPTOR antagonists are now well established in the treatment of hypertension but the mechanism by which they reduce blood pressure is not understood1. There is clearly more involved than an immediate blockade of the cardiovascular β-adrenergic receptors, since intravenous (i.v.) infusion of propranolol in man reduces cardiac output but has no effect on arterial blood pressure2,3. The full hypotensive effect of β-adrenergic blockers is delayed4, and is associated with a reduction in peripheral resistance2,3. The hypotensive action of these drugs is nevertheless predominantly related to their common property of β-adrenergic receptor blockade, as they all produce similar falls in blood pressure5 despite their differing ancillary properties6 and effects on plasma renin activity7. It has been suggested that the hypotensive effect of propranolol is due to a central inhibition of sympathetic activity, since i.v. propranolol reduces preganglionic sympathetic nerve activity in rabbits8. But practolol, an effective antihypertensive which penetrates the central nervous system poorly9, has no such acute effect10. The possibility has yet to be considered that the hypotensive action common to all β-adrenoceptor antagonists is directly related to a slowly developing reduction in sympathetic activity and hence in peripheral resistance. Long term increases or decreases in the activity of sympathetic neurons are specifically reflected by changes in the concentration of the noradrenaline-synthesising enzymes tyrosine hydroxylase and dopamine β-hydroxylase contained in the cells11. We report here that prolonged treatment with β-adrenoceptor antagonists causes a slow-onset reduction in the concentration of these enzymes in the superior cervical ganglia of rabbits. This decrease in sympathetic activity may in part explain the hypotensive effect of long-term β-blockade.

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RAINE, A., CHUBB, I. Long term β-adrenergic blockade reduces tyrosine hydroxylase and dopamine β-hydroxylase activities in sympathetic ganglia. Nature 267, 265–267 (1977). https://doi.org/10.1038/267265a0

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