Lower vascular tone and larger plasma volume in Parkinson's disease with orthostatic hypotension

Abstract

Here, we test the role of two other possible factors: 1) a reduced peripheral vasoconstriction (which may contribute because PD includes a generalized sympathetic denervation); and 2) an inadequate plasma volume (which may explain why plasma volume expansion can manage orthostatic hypotension in PD). We included 11 PD patients with orthostatic hypotension (PD ϩ OH), 14 PD patients without orthostatic hypotension (PD Ϫ OH), and 15 agematched healthy controls. Leg blood flow was examined using duplex ultrasound during 60°head-up tilt. Leg vascular resistance was calculated as the arterial-venous pressure gradient divided by blood flow. In a subset of 9 PD ϩ OH, 9 PD Ϫ OH, and 8 controls, plasma volume was determined by indicator dilution method with radiolabeled albumin ( 125 I-HSA). The basal leg vascular resistance was significantly lower in PD ϩ OH (0.7 Ϯ 0.3 mmHg·ml Ϫ1 ·min) compared with PD Ϫ OH (1.3 Ϯ 0.6 mmHg·ml Ϫ1 ·min, P Ͻ 0.01) and controls (1.3 Ϯ 0.5 mmHg·ml Ϫ1 ·min, P Ͻ 0.01). Leg vascular resistance increased significantly during 60°head-up tilt with no significant difference between the groups. Plasma volume was significantly larger in PD ϩ OH (3,869 Ϯ 265 ml) compared with PD Ϫ OH (3,123 Ϯ 377 ml, P Ͻ 0.01) and controls (3,204 Ϯ 537 ml, P Ͻ 0.01). These results indicate that PD ϩ OH have a lower basal leg vascular resistance in combination with a larger plasma volume compared with PD Ϫ OH and controls. Despite the increase in leg vascular resistance during 60°h ead-up tilt, PD ϩ OH are unable to maintain their blood pressure.Parkinson's disease; orthostatic hypotension; leg vascular resistance; plasma volume; head-up tilt SYMPTOMATIC AND ASYMPTOMATIC orthostatic hypotension (OH) is present in 30 -60% of patients with Parkinson's disease (PD) (15) and negatively correlated with quality of life (32). In elderly, OH is associated with cardiovascular morbidity and mortality (31, 33). The pathophysiology of OH in PD remains incompletely understood. Until now, the focus has been primarily on impairment of central mediated vasoconstrictor mechanisms. PD patients have a reduced baroreflex cardiovagal function, denervation of the heart, low norepinephrine levels, and no increment in norepinephrine levels during orthostatic challenges (14, 39). However, baroreflex failure and cardiac sympathetic denervation contribute to but cannot fully explain OH in PD (14, 16). During orthostatic challenges peripheral vasoconstriction contributes to maintain blood pressure via a central mediated vasoconstrictor mechanism, i.e., baroreflex, and local vasoconstrictor mechanisms, such as the venoarteriolar axon reflex (21) and the myogenic response (11). Since in PD a generalized rather than a central sympathetic denervation is present (40), central and local mediated peripheral vasoconstriction might be affected and, thereby, might play an important role in the pathophysiology of OH in PD.Furthermore, a lower plasma volume may be another contributing factor to OH in PD. This assumption is based on the important role of the s...

Initial circulatory response to active standing in Parkinson's disease without typical orthostatic hypotension

“…With respect to the first possibility, Andersen et al found that, in PD patients without symptoms or signs of autonomic dysfunction, local reflexes did not differ from those +3 +5 +7 +9 +11 +13 +15 +17 +19 +21 +23 +25 +27 +29 75 50 150 B 120 100 80 60 125 100 mmHg bpm MSR -9 -7 -5 -3 -1 +1 +3 +5 +7 +9 +11 +13 +15 +17 +19 +21 +23 +25 +27 +3 +5 +7 +9 +11 +13 +15 +17 +19 +21 +23 +25 +27 +29 60 80 100 120 PD -TOH YHC . This finding was corroborated by Fusina et al 23 and more recently by Groothuis et al 8 Regarding the second possibility, it is noteworthy that baroreflex function assessment has concentrated on baroreceptor-HR reflex, even though PVR control is of greater importance during orthostatic stress. In the same manner, this attention has focused on the sensitivity of the baroreflex response and not in its latency.…”

“…Peripheral sympathetic vasoconstriction, in part baroreflex-mediated, is responsible for the rebound of BP from SBP b to SBP os following AS 1,18 . Local reflexes are involved as well in this PVR increment 8,19,20 . Except for the venoarteriolar response (VAR) in those aged over 75 years, both central and local responses are independent of age in healthy subjects 1,19,21 .…”

“…These CVA differences could account for the reduced reporting of OS in PD 6 . Autonomic dysfunction in PD is associated with a generalized sympathetic denervation 8 . Recently, it has been reported that PD patients with TOH (PD+TOH) have a lower basal leg vascular resistance, which might suggest that sympathetic denervation is more pronounced in PD+TOH than in PD patients without TOH (PD-TOH) 8 .…”

“…Autonomic dysfunction in PD is associated with a generalized sympathetic denervation 8 . Recently, it has been reported that PD patients with TOH (PD+TOH) have a lower basal leg vascular resistance, which might suggest that sympathetic denervation is more pronounced in PD+TOH than in PD patients without TOH (PD-TOH) 8 . Yet, Oka et al documented that latent cardiac and vasomotor sympathetic dysfunction occurs in PD-TOH patients 9 .…”

“…Yet, Oka et al documented that latent cardiac and vasomotor sympathetic dysfunction occurs in PD-TOH patients 9 . While the hemodynamic response to orthostatic stress has been already evaluated in PD-TOH 8 , IOH can be documented only by continuous beat-to-beat BP monitoring during AS 1 . Consequently, in this study, we assessed beat-tobeat the initial hemodynamic response to AS in PD-TOH and compared this response to that seen in young healthy controls (YHC).…”