Sympathetic Nervous System Involvement in Essential Hypertension: Increased Platelet Noradrenaline Coincides with Decreased β-Adrenoreceptor Responsiveness

Abstract

Platelet catecholamine content may reflect integrated plasma catecholamine concentrations over time. The present study aimed at examining sympathetic nervous system (SNS) involvment in essential hypertension by assessing platelet noradrenaline (NA) and typically β-adrenoreceptor mediated responses to adrenaline (A) infusion as indices of sympathetic tone. Healthy white men were recruited by public advertising and screening (mean ± SD): Hypertensives (n = 13, sitting blood pressure [BP] 153 ± 13/106 ± 7 mmHg, age 34 ± 5 years, weight 83 ± 10 kg) were compared to normotensives (n = 13, sitting BP 114 ± 9/75 ± 9 mmHg, age 30 ± 6 years [n.s.], weight 82 ± 9 kg [n.s.]). Loss of platelet granular contents (including NA) prior to analysis was minimized by studying young subjects (age range 20–40 years, minimal atherosclerosis), using arterial blood sampling, and processing blood immediately. These procedures resulted in plasma β-thromboglobulin and platelet factor 4 levels which were not significantly different between groups. Sympathetic activation resulting from stress was minimized by not labelling subjects as either hypertensive or normotensive. Mean arterial platelet NA content was significantly higher in hypertensives (64 ± 31 pg/mg of platelet weight) compared to normotensives (43 ± 20 pg/mg, p < 0.05) both at baseline and following 35% expansion of the circulating platelet pool by A infusion (p < 0.05) and correlated with arterial NA in the hypertensives (r = 0.79, p < 0.002) but not in the normotensives (r = 0.04, n.s.). Similar increases in platelet and plasma A during infusion in both groups suggest unchanged platelet uptake capacity and plasma clearance in the hypertensive group. The hypertensives had both increased heart rate (p < 0.02) and pulse pressure (p < 0.001) compatible with increased sympathetic drive. Changes in heart rate, serum glucose and serum phosphate, typically β-adrenoreceptor responses to A infusion, were attenuated in the hypertensives (p < 0.05 for all), compatible with down-regulation of β-adrenoreceptors secondary to chronically increased sympathetic tone. Thus, increased platelet NA found in this study seems to be related to plasma noradrenaline concentrations and coincides with other evidence of raised SNS activity in essential hypertension. Catecholamine content in properly collected platelets may prove to be a good marker of the integrated sympathetic tone in studies of hypertensives.

Key Words:

• adrenaline
• blood platelets
• blood pressure
• β-receptor responses
• hypertension
• noradrenaline
• platelet release
• sympathetic activity