Abstract

Prehypertension is associated with increased risk of hypertension and cardiovascular disease (CVD). The physiological mechanisms underlying this risk are unknown, and the appropriate therapeutic approach to this preclinical but high‐risk population remain unclear. Previous studies have shown increased resting sympathetic nerve activity, as well as augmented blood pressure (BP) responses during mental stress in prehypertension, suggesting autonomic dysregulation at rest and during stress. We hypothesized that compared to normotensive controls (BP ≤ 120/80 mm Hg), prehypertensives (BP 120/80–139/89 mm Hg) have impaired arterial baroreflex sensitivity (BRS), the major feedback system regulating autonomic tone in response to BP changes, as well as increased neurocardiovascular reactivity to mental stress. Twenty‐two participants were studied; 12 otherwise healthy prehypertensives (age 35±6 years) were compared to 10 normotensive controls (age 32±6 years,) matched for age, gender, race, and body mass index. We recorded muscle sympathetic nerve activity (MSNA) using microneurography, beat‐to‐beat arterial BP, and heart rate (HR) via continuous EKG during five minutes of supine rest and three minutes of mental stress induced via mental arithmetic. We measured resting arterial baroreflex sensitivity (BRS) using the modified oxford technique in which IV boluses of nitroprusside and phenylephrine were infused to manipulate arterial BP. The slope of the linear relationship between diastolic BP and MSNA burst incidence was assessed for sympathetic BRS, and between change in systolic BP and R‐R interval for cardiovagal BRS. As expected, baseline systolic BP (130±7 vs. 117±8 mmHg) and diastolic BP (87±7 vs. 74±8 mmHg) were significantly higher in prehypertensives (p<0.001), but HR (70±10 vs. 66±13 beats/min, p>0.05) was comparable between the groups. Resting MSNA (25±12 vs. 18±10 bursts/min) tended to be higher in prehypertensives (p=0.08). Sympathetic BRS was comparable between the groups at rest, but cardiovagal BRS (13±10 vs. 22±10 ms/mmHg) was significantly lower in prehypertensives (p=0.03). During mental arithmetic, minute‐by‐minute increases in BP, HR and MSNA did not differ between the groups. There was a significant positive correlation between the diastolic BP response during mental stress and resting cardiovagal BRS (r=0.703, p=0.016), and with sympathetic BRS (r=0.795, p=0.010) within the prehypertensive group. However, there was no significant relationship between BP responses during mental stress with cardiovagal (r=0.126, p=0.766) or sympathetic BRS (r=0.287, p=0.581) in normotensive controls. These findings suggest that an early impairment of arterial BRS may be present in prehypertension and may modulate BP responses to stress, contributing to increased hypertension and CVD risk.Support or Funding InformationSupported by NIH HL‐098744, NIH DK‐00756, VA Merit I01CX001065, AHA 15CSA24340001This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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