Rf Whelan

The local metabolic action of adrenaline on skeletal muscle in man.

The relation between the vascular and the metabolic effects of adrenaline has recently been emphasized by Lundholm (1956), who has advanced the proposition that the dilator action of adrenaline on the vessels of skeletal muscle is indirect and mediated by release of lactic acid. Although it is well known that adrenaline promotes lactic acid formation in animal muscle (Griffith, 1951; Lundholm, 1956), evidence on this point in the human is lacking. Several investigators have suggested that adrenaline may release lactic acid from human skeletal muscle (Barcroft & Cobbold, 1956) but Hildes, Purser & Sherlock (1949) were unable to demonstrate a direct metabolic action of adrenaline on the muscles of the lower limb in man. They could find no increase in the lactic acid level of the femoral venous blood and no reduction in glycogen content of biopsy specimens from gastrocnemius muscle following infusions of adrenaline into the femoral artery. Using adrenergic blocking agents, de la Lande & Whelan (1959) have demonstrated a potent dilator action of adrenaline when administered locally in the forearm, and the findings are consistent with the view that a metabolite released from muscle might be responsible for this effect. The possibility of a direct local metabolic effect of adrenaline on human muscle has been re-examined in the upper limb where more precise correspondence ofinfused tissue and sampling site can be ensured than in the leg. Changes in the levels of a number of metabolites have been found in the venous effluent, which indicate a direct glycogenolytic action of adrenaline on human skeletal muscle.

Cardiovascular actions of angiotensin in man

Abstract Angiotensin exerts a direct action on the smooth muscle of the blood vessels of the human hand and forearm, the latter being the more sensitive. In addition, angiotensin has a central sympathetic stimulating action which, in the case of the hands and feet, is responsible for all of the vasoconstriction seen on intravenous administration. The central action does not play a significant part in the pressor effect of angiotensin given intravenously for short periods of time. In contrast to observations in animals, angiotensin in man does not appear to cause release of adrenal medullary hormones, nor does it act on the peripheral sympathetic nerve endings to discharge the transmitter. Angiotensin causes a modest potentiation of the response of the hand vessels to intra-arterial noradrenaline, which is, however, much less marked than that seen with the isolated perfused digital artery. The blood vessels of the hands of patients with renovascular hypertension show a very marked reduction in sensitivity to angiotensin, whereas the sensitivity in patients with essential hypertension is within the normal range. The phenomenon of tachyphylaxis to angiotensin is widely recognized in animals and isolated preparations, but its occurrence or significance has not been investigated in man.

The role of skin and muscle vessels in the response of forearm blood flow to noradrenaline

The response of the forearm blood flow to noradrenaline is often used in the assessment of drug action and of changes in vascular sensitivity in man. There are, however, conflicting reports on the effects of this agent on the forearm vessels. During intravenous infusions, Duncanson, Stewart & Edholm (1949) described a decrease in forearm flow as did Barnett, Blacket, Depoorter, Sanderson & Wilson (1950) while Barcroft & Konzett (1949) noted an increase which they interpreted as a passive response to the rise in blood pressure. Barcroft, Gaskell, Shepherd & Whelan (1954) also described an increase in forearm flow which they attributed to a reflex dilatation in muscle. In the case of adrenaline the response of the total forearm flow has been shown to be the resultant of the differential action of this drug on skin and muscle vessels (Skinner & Whelan, 1962) and the level of skin flow has a marked influence on the pattern of the total response (Whelan & de la Lande, 1963). Little direct information is available on the differential actions of noradrenaline on the various vascular beds which make up the limb circulation. The present study was designed to analyse the effects of this drug on the two major vascular beds in the forearm, namely those of skin and muscle, and particularly to assess the role of the skin circulation in modifying total forearm blood flow responses to this amine.

The role of lactic acid in the vasodilator action of adrenaline in the human limb

Adrenaline given intravenously exerts a dilator action on the muscle vessels of the forearm in man (Allen, Barcroft & Edholm, 1946) and a local vasodilator effect is also seen when adrenaline is infused intra-arterially in the presence of antagonists (de la Lande & Whelan, 1959). The dilator effect is confined to the muscle vessels and on intra-arterial infusion the response may be masked by reduction in skin blood flow (Skinner & Whelan, unpublished). Lundholm (1956) attributes the dilator action of adrenaline in the cat to the release of lactic acid from the muscles and Barcroft & Cobbold (1956) suggest that products of carbohydrate metabolism may be involved. The recent demonstration of a local metabolic effect of adrenaline on human skeletal muscle, with an increased concentration of lactic acid in the venous effluent (de la Lande, Manson, Parks, Sandison, Skinner & Whelan, 1961) prompted the investigation of the role which lactic acid might play in the adrenaline dilatation in human skeletal muscle.