INFLUENCE OF HYPOTHALAMIC-RELEASING HORMONE ON AUTONOMIC NERVOUS SYSTEM DETERMINED BY VARIATIONS IN R-R INTERVALS ON ELECTROCARDIOGRAM (ECG)

Abstract

Hypothalamic hormone is suggested to have an effect on extrapituitary sites. Little information is available about the effects of hypothalamic-releasing hormones on the human autonomic nervous system. Variations in R-R intervals on electrocardiogram (ECG), a parameter of parasympathetic nervous system function, have been used clinically as an indicator of autonomic nervous system dysfunction in various diseases. An attempt was made to determine serial variations in R-R intervals on ECG.
Studies were conducted with 23 healthy controls and 52 patients with Graves' disease. Variations in R-R intervals were expressed as the coefficient of variation of 100 resting heart rates (CV%=SD/Mean x 100, CVq).
Injection of TRH (500μg, iv) to healthy controls produced a significant elevation of CVq (4.37±0.53% before vs. 5.46±0.40% after TRH, p <0.01) within 15 min. A similar result was obtained in patients with Graves' disease. Pretreatment with atropine (0.5mg, div) or pirenzepine hydrochloride (250mg, po) abolished the stimulatory effect of TRH on CVq. Pretreatment with Clofedanol (75mg, po), which is reported to have an inhibitory effect on the meddula oblongata, and hexamethonium bromide (300mg, po), a ganglionic blocker, resulted in a significant reduction in CVq during TRH test. There was no change in plasma catecholamine concentrations following TRH administrations. Intravenous injection of CRF (50μg) produced a significant decrease in CVq. Pretreatment with propranolol (30mg, po) blocked the effect of CRF. On the other hand, iv administration of GRF (50μg) or LHRH (100μg) had no effect on CVq, while normal responses of serum GH, LH and FSH were observed.
In conclusion, TRH stimulates CVq in normal subjects and patients with Graves disease. It is suggested that TRH potentiates the parasympathetic nervous system, regardless of circulating thyroid hormone levels. In contrast, CRF has a suppressive effect on vagal activity in human subjects, probably associated with adrenergic β-effect. Both GRF and LHRH seemed to have little effect on the autonomic nervous system at clinical doses. The present study is the first demonstration that some hypothalamic-releasing hormones affect the autonomic nervous system, as indicated by the variations in R-R intervals on ECG.