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Studies comparing the effects of epinephrine and nor-epinephrine, the two sympathomimetic amines which occur naturally in the mammalian body, show that these two closely related substances differ in many of their pharmacodynamic properties. The metabolic rate in man has been shown to increase after epinephrine (1, 2), whereas there is no significant change produced by nor-epinephrine (2). Systemic administration of epinephrine to man has been shown to result in a decrease in total peripheral resistance (1, 3), indicating that vasodilatation has occurred in many portions of the body; in contrast, nor-epinephrine appears to be predominantly vasoconstrictor in its action, for total peripheral resistance is increased (3).These differences may be manifestations of the specific functions which these substances perform in the body; von Euler (4) believes that nor-epinephrine is the sympathetic mediator for general purposes, while epinephrine acts as an adjuvant for more special functions, especially in regard to metabolic actions.In view of the importance of epinephrine and nor-epinephrine in physiological processes, their occurrence in pheochromocytomas, their use as therapeutic agents, and the possible relation of nor-epinephrine to essential hypertension (3), information regarding their effect on cerebral blood flow and cerebral metabolism is desirable. A preliminary report by Sensenbach, Madison, and Ochs (5) indicates that nor-epinephrine is a powerful cerebral vasoconstrictor. The animal studies upon epinephrine have yielded conflicting results (6-8). Qualitative measurements of cerebral blood flow in man by means of a thermoelectric

Recent observations by this group on the cerebral circulation in hypertension (1) have yielded normal values for cerebral blood flow and cerebral oxygen consumption but a marked increase in cerebrovascular resistance. Since the nature of this excessive vascular tone is obscure, it was felt that studies of its behavior during an acute fall in blood pressure might be of interest. Such studies, furthermore, should be pertinent to the rationale of therapy designed to lower the blood pressure in hypertension, since a fall in blood pressure must necessarily be accompanied by a comparable embarrassment of the cerebral circulation except insofar as the high cerebrovascular tone were capable of compensatory relaxation.Differential spinal sympathetic block, achieved by the injection of dilute procaine solution into the lumbar subarachnoid space (2), produces a considerable fall in the blood pressure of many hypertensive patients, presumably by blocking the sympathetic outflow to the abdomen and lower extremities without loss of skeletal muscle tone. This procedure, therefore, offers a means of studying the response of the cerebral circulation to a drop in blood pressure mediated by dilatation in vascular beds remote from the brain. The use of differential spinal block as a possible screening test in selecting patients for surgical sympathectomy provided an opportunity for undertaking these studies on the cerebral circulation. METHODSMeasurements were made in 17 patients with essential hypertension who were being studied on the medical and surgical services as candidates for surgical sympathectomy. Cerebral blood flow (CBF) was determined by means of the nitrous oxide method, and with this value cerebral metabolism in terms of oxygen consumption (CMRo2) and cerebrovascular resistance (CVR) were calculated as previously described (3, 4). Mean arterial blood pressure (MABP) was read from a damped mercury manometer attached to a needle in the femoral artery. Blood gas analyses were made in the Van Slyke-Neill manometric apparatus (5) and pH was measured at 370anaerobically by means of a glass electrode. Values for plasma C02 tension were calculated by means of a nomogram (5).A fine plastic catheter was introduced into the lumbar subarachnoid space. Needles were then placed in the superior bulb of an internal jugular vein and a femoral artery. The patients rested supine for 30 minutes after which control observations were made. Twenty cc. of procaine hydrochloride (0.2% in physiological saline solution) were then introduced intrathecally, usually resulting in diminution of pain sensibility over the lower extremities and well into the intercostal region. This level of anesthesia was kept relatively constant by the instillation of more procaine as needed. The blood pressure usually fell promptly and sometimes markedly, then showed a tendency to remain at a level somewhat above the lowest point reached. When this stabilization had occurred a second determination of cerebral blood flow was made. In some cases the lowest point was...

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