Modulations of autonomic cardiovascular control following acute alpha-adrenergic treatment in chronic hypotension

Chronic low blood pressure is typically accompanied with symptoms such as fatigue, reduced drive, dizziness, headaches and cold limbs. Alterations in autonomic cardiovascular regulation are assumed to be involved in the etiology of this condition, that is, increased baroreflex sensitivity (BRS) as well as reduced sympathetic and augmented parasympathetic influences on cardiovascular regulation. In this study, the acute effects of the blood pressure-enhancing alpha-adrenergic agonist, midodrine, on autonomic cardiovascular control were investigated in 50 hypotensive persons (mean blood pressure 96/61 mmHg) based on a placebo-controlled double blind design. BRS was determined using sequence analysis. Spectral analysis of heart rate variability was carried out to quantify sympathetic and parasympathetic cardiac control. Parameters were obtained at rest and during mental stress. Drug application led to marked increases in blood pressure, BRS and respiratory sinus arrhythmia ( RSA), whereas heart rate and power in the low frequency (LF) band of the heart rate variability spectrum decreased. The augmentation of RSA and reduction of LF power indicate a shift of the sympathovagal balance toward increased parasympathetic and reduced sympathetic influences on heart rate. Like the increase in BRS, these modulations represent a counter-regulatory autonomic response to the blood pressure elevation, which is initiated to return blood pressure to the initial value or to an individual set point. The finding challenges the use of alpha-sympathomimetics in the treatment of chronic hypotension as they may not reduce but may instead exacerbate the autonomic dysbalance related to this condition. Hypertension Research (2009) 32, 938-943; doi: 10.1038/hr.2009.115; published online 7 August 2009