Cerebral Oxidative Metabolism in Hypertension

Abstract

1. The evidence is now overwhelming that so-called ‘essential’ hypertension in man, i.e. high systemic arterial pressure for no apparent cause, is commonly initiated by increased efferent sympathetic activity directed to the cardiovascular system. Eventually structural and other changes take place in the heart, kidneys and blood vessels. These may reinforce, augment and even conceal the initially neurogenic background. The cause of the increased sympathetic activity remains in dispute, but it is probably not psychological in most cases. 2. The brain has a high requirement for energy — twice that of the heart, at rest. In the normotensive adult, the brain's needs are met almost exclusively by the oxidation of glucose. This results in a cerebral respiratory quotient for the brain of approximately unity. The brain can utilize other materials, notably ketones, as it does to a considerable extent in the fetus. It retains this capability in adult life, even though normal adults do not make use of it. 3. In human hypertension the cerebral respiratory quotient falls in proportion to the rise of arterial pressure, indicating the consumption of other fuels in addition to glucose. β-Hydroxybutyrate is certainly one of these, but fatty acids may also be utilized. 4. A similar or greater reduction of cerebral respiratory quotient than in essential hypertension is seen in chronic cerebrovascular disease and in chronic heart failure in man. This raises the possibility that although cerebral blood flow is only slightly reduced in hypertensive patients at rest, the cerebral circulation is potentially under threat. The change in the pattern of oxidative metabolism may be looked upon as an adaptation to the threat. This would fit in with strong epidemiological and pathological evidence linking hypertension with cerebral, especially vertebrobasilar, atheroma. 5. Many of the pathophysiological changes in essential hypertension have parallels in the spontaneous hypertensive rat and its stroke-prone variant. Such rats have an impaired cerebral blood supply. Infarctions are easily produced by arterial occlusions which have little adverse effect on Wistar—Kyoto rats. Spontaneous hypertensive rats and stroke-prone spontaneous hypertensive rats also have reduced cerebral glucose utilization, which mirrors the situation in essential hypertension. 6. The Cushing response — threatened medullary ischaemia activating sympathetic vasomotor efferent nerves — could provide the mechanism by which chronic borderline or intermittent cerebral circulatory inadequacy passed a signal to activate sympathetic efferent nerves, either directly or through altered brain metabolism. 7. Other interpretations are possible, but the evidence of this review suggests that further investigation of cerebral oxidative metabolism in hypertension and in related conditions may shed light on the still elusive aetiology of essential hypertension.