Mechanisms of orthostatic hypotension and supine hypertension in Parkinson disease

Abstract

Non-motor aspects of Parkinson disease (PD) are now recognized to be important both clinically and scientifically. Among these facets are abnormalities in blood pressure regulation. As much as 40% of PD patients have orthostatic hypotension (OH), which is usually associated with supine hypertension (SH). Symptoms of OH range from light-headedness to falls with serious trauma. SH, while typically asymptomatic, poses a significant increased risk for cardiovascular morbidity and mortality. Neuroimaging, neurochemical, and neuropharmacological studies indicate cardiac and extra-cardiac sympathetic noradrenergic denervation and baroreflex failure in virtually all PD patients with OH, and cardiac sympathetic denervation has been confirmed histopathologically. Mechanisms of SH in PD+OH remain poorly understood. The diurnal blood pressure profile shows increased variability that is correlated with decreased baroreflex gain and with increased morbidity and mortality. Treatment should be individually tailored according to the timing of OH or SH, using primarily short-acting sympathomimetic medications in the daytime for OH and short-acting antihypertensive in the nighttime for SH. Future research is needed to understand better and attenuate blood pressure fluctuations through manipulations that improve baroreflex function.

Fig. 1

Heart rate and blood pressure responses in the 4 phases of the Valsalva maneuver in (left) a control subject and (right) a patient with Parkinson disease and orthostatic hypotension. Neurogenic orthostatic hypotension is characterized by a progressive decline in blood pressure in phase II (arrow), slow recovery of blood pressure in phases III and IV and absence of overshoot in pressure above baseline in phase IV (thick black line).

Fig. 2

Cardiac positron emission tomographic scans after intravenous injection of 6-[¹⁸F]fluorodopamine (6-[¹⁸F]FDA) or the perfusion imaging agent [¹³N]-ammonia ([¹³N]NH3) in patients with pure autonomic failure (PAF), multiple system atrophy (MSA), Parkinson disease with neurogenic orthostatic hypotension (NOH) and normal volunteers (NV). Note absence of detectable 6-[¹⁸F]fluorodopamine-derived radioactivity in the left ventricular myocardium, despite normal perfusion as indicated by [¹³N]-ammonia-derived radioactivity, in the patient with Parkinson disease.

Fig. 3

Group comparison between subjects with pure autonomic failure (PAF), multiple system atrophy (MSA), Parkinson disease with neurogenic orthostatic hypotension (NOH) and normal volunteers (NV) in (A) plasma dihydroxyphenylglycol glycol (DHPG) responses (means±SEM) to tyramine infusion; (B) plasma norepinephrine (NE) responses (means±SEM) to isoproterenol infusion; (C) Skeletal muscle microdialysate concentrations (means±SEM) of dihydroxyphenylglycol glycol (DHPG); and (D) change in systolic blood pressure (PBs) to yohimbine or trimethaphan infusion.

Fig. 4

24-hour blood pressure monitoring of a 73 years old patients with Parkinson disease and orthostatic hypotension.

Fig. 5

Log baroreflex slope, derived from heart rate response to blood pressure changes in patients with Parkinson disease with orthostatic hypotension (PD+OH), Parkinson disease without orthostatic hypotension (PD no OH) an healthy volunteers (Normal).