AHA/ACC-defined stage 1 hypertensive adults do not display cutaneous microvascular endothelial dysfunction

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 319; no. 3; pp. H539 - H546
• Main Authors: Dillon, Gabrielle A, Greaney, Jody L, Shank, Sean, Leuenberger, Urs A, Alexander, Lacy M
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.09.2020
• Series: Translational Physiology
• Subjects: Acetylcholine; Adult; Adults; Aged; Arginine; Blood Pressure; Cardiology; Circadian Rhythm; Dilation; Dipping; Doppler effect; Endothelium; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiopathology; Female; Humans; Hypertension; Hypertension - classification; Hypertension - diagnosis; Hypertension - physiopathology; Male; Microdialysis; Microvasculature; Microvessels - metabolism; Microvessels - physiopathology; Middle Aged; NG-Nitroarginine methyl ester; Night; Nighttime; Nitric oxide; Nitric Oxide - metabolism; Perfusion; Retrospective Studies; Severity of Illness Index; Skin - blood supply; Time Factors; Vasodilation; blood pressure; endothelium-dependent dilation; intradermal microdialysis; nitric oxide; laser-Doppler flowmetry
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00179.2020

In 2017, the American Heart Association (AHA) and American College of Cardiology (ACC) redefined stage 1 hypertension to systolic blood pressure (BP) 130-139 mmHg or diastolic BP 80-89 mmHg; however, the degree to which microvascular endothelial dysfunction is evident in adults with stage 1 hypertension remains equivocal. We tested the hypotheses that cutaneous microvascular endothelial dysfunction would be present in adults with stage 1 hypertension (HTN1) compared with normotensive adults (NTN; BP <120/<80 mmHg) but would be less severe compared with adults with stage 2 hypertension (HTN2; systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg) and that this graded impairment would be mediated by reductions in nitric oxide (NO)-dependent dilation. This retrospective analysis included 20 NTN (5 men; 45-64 yr; BP 94-114/60-70 mmHg), 22 HTN1 (11 men; 40-74 yr; BP 110-134/70-88 mmHg), and 44 HTN2 (27 men; 40-74 yr; BP 128-180/80-110 mmHg). BP and nocturnal dipping status were also assessed using 24-h ambulatory BP monitoring. Red cell flux (laser Doppler flowmetry) was measured during intradermal microdialysis perfusion of acetylcholine (ACh; 10 to 10 M) alone and concurrently with the nonspecific nitric oxide (NO) synthase inhibitor -nitro-l-arginine methyl ester (l-NAME; 15 mM). ACh-induced dilation was impaired in HTN2 ( < 0.01), but not in HTN1 ( = 0.85), compared with NTN. Furthermore, reductions in NO-dependent dilation were evident in HTN2 ( < 0.01) but not in HTN1 ( = 0.76). Regardless of BP, endothelium-dependent dilation was impaired in nondippers (nighttime drop in systolic BP <10%) compared with dippers (nighttime drop in systolic BP ≥10%, < 0.05). In conclusion, functional impairments in NO-mediated endothelium-dependent dilation were not evident in HTN1. However, regardless of BP classification, the lack of a nocturnal dip in BP was associated with blunted endothelium-dependent dilation. This is the first study to pharmacologically assess the mechanistic regulation of endothelial function in adults with hypertension, classified according to the 2017 clinical guidelines set for by the American Heart Association (AHA) and American College of Cardiology (ACC). Compared with that in normotensive adults, nitric oxide-mediated endothelium-dependent dilation is impaired in adults with stage 2, but not stage 1, hypertension. Adults lacking a nighttime dip in blood pressure demonstrated reductions in endothelium-dependent dilation.