THE EFFECTS OF AUTONOMIC NERVOUS SYSTEM INHIBITION ON THE CIRCULATORY RESPONSE TO MUSCULAR EXERCISE.

One of the primary functions performed by the cardiovascular system is the delivery of oxygen and metabolic substrates to the peripheral tissues during varying levels of their activity. Accordingly , the manner in which the circulation is altered during muscular activity and the consideration that the cardiovascular response is mediated through the interaction of a number of mechanisms , prominent among which is the activity of the autonomic nervous system, are of interest. The present investigation was undertaken in an attempt to clarify the role of this mechanism in normal human subjects by determining the manner in which inhibition of the parasympathetic and the sympathetic divisions, or both, affected the circulatory response to exercise. Two pharma-cologic agents were employed to produce functional inhibition of the autonomic nervous system; atro-pine was used to inhibit the parasympathetic division , and guanethidine, an effective adrenergic blocking agent (1), was used to interfere with the activity of the sympathetic division. METHODS The investigations were carried out on six healthy male subjects whose ages ranged from 18 to 20 years. All studies were performed in the supine position, and measurements of heart rate, cardiac output, arterial blood pressure, and oxygen consumption were made at rest and during exercise in the four investigations performed on each subject. The first (control study) was performed without prior drug administration. Forty-five minutes after its completion, 2 mg of atropine sulfate was administered intravenously, and 5 minutes later the resting measurements were repeated, followed immediately by exercise. After these two studies oral guanethidine administration was begun at a daily dosage of 10 mg, which was progressively increased by 5 mg increments every other day for a period of 21 to 26 days. The maximum daily dosage reached ranged from 50 to 85 mg for each subject. The subjects were questioned about the side effects of guanethidine, and supine and standing blood pressures were recorded twice daily. The third study was performed at the end of the period of guan-ethidine administration while subjects were receiving the maximal doses. Forty-five minutes after completion of the third study, 2 mg of atropine sulfate was again administered intravenously, and five minutes later the fourth study was begun. Each subject had been thoroughly familiarized with the laboratory, the equipment, and the experimental procedure prior to the study, and all observations were carried out with the subj ects in the postabsorptive state. The control resting measurements …