Catecholamines and hypertension.

Ever since the demonstration that the active principle in the adrenal medulla can raise blood pressure (Oliver & Schafer, 1895), catecholamines have been implicated in the hypertensive diseases. The identity of noradrenaline as the neurotransmitter of sympathetic nerves (von Euler, 1946) and the demonstration that an injection of this catecholamine can produce cardiovascular changes similar to those observed in hypertensive patients (Goldenberg, Piner, Baldwin, Greene & Roh, 1948) pointed to an abnormal sympathetic nervous activity in this disease. Possibly the most compelling evidence of the involvement of the sympathetic nervous system and the adrenal medulla is the demonstration that drugs affecting the adrenergic systems are therapeutically useful in the treatment of hypertensive diseases. These anti-hypertensive drugs act at a variety of sites in the adrenergic system: the uptake, storage, release and metabolism of noradrenaline and on adrenergic receptors. Guanethidine depletes nor-adrenaline in the peripheral sympathetic nerves, reserpine depletes catecholamines peripherally and in the brain; a-methyldopa is metabolized to a false neurotransmitter, a-methylnoradrenaline; pro-pranolol blocks p-adrenoreceptors; clonidine stimulates a-adrenoreceptors in the brain. The fact that drugs influencing the disposition of the neurotransmitter noradrenaline alleviate hyper-tension does not necessarily mean that sympathetic nerve dysfunction is the primary cause of hyper-tension, but it is an important factor. The degree of involvement of sympathetic nerves may vary with different types of hypertension and during different phases of the development of hypertensive diseases. The development of anti-hypertensive drugs that act on the sympathetic nervous system was made possible by the interaction of basic and clinical sciences. These drugs increased the survival time of patients with hypertensive diseases dramatically and their introduction represents a major achievement in modern medicine. In hypertension produced by phaeochromocyto-mas there is a marked elevation in the excretion of noradrenaline and its metabolites (Crout, Pisano & Sjoerdsma, 1961). However, attempts to relate abnormal excretion of catecholamines in other types of hypertension were contradictory (de Champlain, 1972). It is likely that in hypertension there is an aberration in catecholamine metabolism in local but critical sites in the peripheral andlor central sympathetic nerves. This then would not be reflected in detectable elevation of catecholamine or its metabolites since urinary excretion represents metabolism of these amines in the entire body. Storage, release and metabolism of catecholatnines In the past decade or so there have been great advances in our knowledge concerning the pharma-cology, physiology and biochemistry of the sympathetic (catecholamine-containing) nervous system (Axelrod, 1973). With …