The role of plasma noradrenaline in health and disease

This paper proposes that plasma noradrenaline plays a central role in the physiology and pathophysiology of the macrocirculation, the heart, veins and arteries. The proposal stems, in the final analysis, from the finding that noradrenaline dilates the canine lateral saphenous vein when it is released from its microcirculation, the vasa venarum. The concentration threshold of the effect is estimated to be at least eight times lower than the threshold of the constrictor effect of intralumenal noradrenaline. Combined with other evidence, the finding indicates that, contrary to opinion, plasma noradrenaline has an effective β₁-agonist hormonal effect on the macrocirculation, at normal concentrations. It also indicates that noradrenaline has a bi-polar effect. The reason it has that effect is that noradrenaline is a primary biological stimulus and like all primary stimuli investigated to date, it can be expected to have two cross-inhibitory components, commonly referred to as excitor and lateral inhibitory. When examined, neuronal noradrenaline shows the features characteristic of excitor components in general and plasma noradrenaline shows those characteristic of inhibitory components. The most significant of the latter is that inhibitory components are the most potent physiological modulators of excitor components. A striking example of that modulation effect occurs in smooth muscle contraction where muscles contracted by neuronal noradrenaline stimulation appear to be incapable of relaxing without stimulation by plasma noradrenaline-hence the proposition that vascular stenosis and cardiospasm are caused by a pathological loss of plasma noradrenaline stimulation. By triggering turbulence, cholesterol plaques increase the arterial microcirculatory flow and so increase the β₁-agonist effect of plasma noradrenaline. This paper proposes that this cholesterol driven increase in the microcirculatory effect of plasma noradrenaline is the cause of the arteriosclerotic syndrome, a proposition that is consistent with the success of beta-blockade in treating manifestations of the syndrome. The paper concludes by examining a variety of conditions, including dissecting aneurysms, dilator cardiac failure, angina, myocardial infarction, hypertension, eclampsia and cirrhosis and pointing out that all of them, like varicose veins, show evidence consistent with having been caused by a turbulence induced increase in a β₁-agonist stimulatory effect of microcirculatory plasma noradrenaline.