PRESSOR SUBSTANCES FROM THE BODY FLUIDS OF MAN IN HEALTH AND DISEASE

1. Extracts of human blood plasma, ascitic and cerebrospinal fluids have been shown to contain a substance or substances which have a prolonged and powerful pressor action when injected into test animals. 2. The chemical properties of the substance suggest those of an organic base. It is extracted with alcohol, soluble in water and acetone, extracted from water by chloroform, and probably is but slightly heat-stable. The plasma colloids seem to hold the substance in a bound state since it does not appear in the ultrafiltrate and is liberated on coagulation of the colloids by alcohol. Coagulation alone of the blood does not cause the substance to be formed. 3. Its action suggests that its pressor effect is brought about by mediation of the central nervous system. This inference was drawn from the following observations. (a) The functional intactness of the central nervous system is essential in order that pressor responses be obtained. Unanesthetized animals exhibit greater vascular responses than do anesthetized. (b) Pithing animals completely abolishes the response. Progressive ablation of the brain to the level of the hind brain does not alter the response, but below this level, injury abolishes the activity of the extract. (c) Some substance in the extract sensitizes the mechanism responsible for the carotid sinus reflex. (d) There is no parallelism between the response to peripherally acting drugs and pressor extracts. (e) Removal of the adrenal glands does not affect its character. 4. The rise in blood pressure appears to be due especially to constriction of the arteries in the splanchnic region. 5. Assay of the pressor extracts is made difficult because of the dependence of the vascular response on the functional state of the central nervous system. The carotid sinus reflex and stimulation with carbon dioxide-air mixtures have proved most useful means for the estimation of this functional state. It has been pointed out that the vascular responses to extract, stimulation of the carotid sinus, and inhalation of carbon dioxide-air vary greatly during the course of an experiment on anesthetized animals. This natural history of the vascular responses has been described. 6. No evidence has been produced by the method employed that the amount of this pressor substance is increased in the blood or spinal fluid of patients with hypertension of varied pathogenesis (nephritic hypertension, essential hypertension, malignant hypertension, eclampsia, and pituitary basophilism).