TY - JOUR
T1 - Microvascular β-Adrenergic Receptor-Mediated Vasodilation Is Attenuated in Adults with Major Depressive Disorder
AU - Greaney, Jody L.
AU - Darling, Ashley M.
AU - Mogle, Jacqueline
AU - Saunders, Erika F.H.
N1 - Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - BACKGROUND: Major depressive disorder (MDD) is associated with sympathetic overactivity and alterations in peripheral adrenergic receptor function; however, no studies have directly assessed vasoconstrictor responsiveness in adults with MDD. We tested the hypotheses that β-adrenergic receptor-mediated vasodilation would be blunted in adults with MDD compared with healthy nondepressed adults (HA) and would functionally contribute to exaggerated norepinephrine-induced vasoconstriction. METHODS: In 13 HA (8 female; 24±4 years) and in 12 adults with MDD (8 female; 22±3 yrs), red blood cell flux was measured during graded intradermal microdialysis perfusion of the β-adrenergic receptor agonist isoproterenol (10−10 to 10−4 mol/L) and, separately, during the perfusion of norepinephrine (10−12 to 10−2 mol/L), alone and in combination with the β-adrenergic receptor antagonist propranolol (2 mmol/L). Nonadrenergic vasoconstriction was assessed via perfusion of angiotensin II (10−12 to 10−4 mol/L). RESULTS: Isoproterenol-induced vasodilation was blunted in adults with MDD (188.9±70.1 HA versus 128.3±39.4 au MDD, P=0.025). Net norepinephrine-induced vasoconstriction was exaggerated in adults with MDD (−0.16±0.54 HA versus -0.75±0.56 au MDD, P=0.014); however, there were no group differences in angiotensin II–induced vasoconstriction. Propranolol potentiated norepinephrine-induced vasoconstriction in HA (−0.16±0.54 norepinephrine versus −1.60±1.40 au propranolol, P<0.01) but had no effect in adults with MDD (−0.75±0.56 norepinephrine versus −1.58±1.56 au propranolol, P=0.08). CONCLUSIONS: β-adrenergic receptor-mediated microvascular vasodilation was blunted in adults with MDD and contributed to exaggerated adrenergic vasoconstriction. The relative loss of the vasoprotective effect of β-adrenergic receptor-mediated vasodilation may contribute to increased peripheral resistance, thereby driving the development of hypertension in adults with MDD.
AB - BACKGROUND: Major depressive disorder (MDD) is associated with sympathetic overactivity and alterations in peripheral adrenergic receptor function; however, no studies have directly assessed vasoconstrictor responsiveness in adults with MDD. We tested the hypotheses that β-adrenergic receptor-mediated vasodilation would be blunted in adults with MDD compared with healthy nondepressed adults (HA) and would functionally contribute to exaggerated norepinephrine-induced vasoconstriction. METHODS: In 13 HA (8 female; 24±4 years) and in 12 adults with MDD (8 female; 22±3 yrs), red blood cell flux was measured during graded intradermal microdialysis perfusion of the β-adrenergic receptor agonist isoproterenol (10−10 to 10−4 mol/L) and, separately, during the perfusion of norepinephrine (10−12 to 10−2 mol/L), alone and in combination with the β-adrenergic receptor antagonist propranolol (2 mmol/L). Nonadrenergic vasoconstriction was assessed via perfusion of angiotensin II (10−12 to 10−4 mol/L). RESULTS: Isoproterenol-induced vasodilation was blunted in adults with MDD (188.9±70.1 HA versus 128.3±39.4 au MDD, P=0.025). Net norepinephrine-induced vasoconstriction was exaggerated in adults with MDD (−0.16±0.54 HA versus -0.75±0.56 au MDD, P=0.014); however, there were no group differences in angiotensin II–induced vasoconstriction. Propranolol potentiated norepinephrine-induced vasoconstriction in HA (−0.16±0.54 norepinephrine versus −1.60±1.40 au propranolol, P<0.01) but had no effect in adults with MDD (−0.75±0.56 norepinephrine versus −1.58±1.56 au propranolol, P=0.08). CONCLUSIONS: β-adrenergic receptor-mediated microvascular vasodilation was blunted in adults with MDD and contributed to exaggerated adrenergic vasoconstriction. The relative loss of the vasoprotective effect of β-adrenergic receptor-mediated vasodilation may contribute to increased peripheral resistance, thereby driving the development of hypertension in adults with MDD.
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U2 - 10.1161/HYPERTENSIONAHA.122.18985
DO - 10.1161/HYPERTENSIONAHA.122.18985
M3 - Article
C2 - 35232218
AN - SCOPUS:85128488913
SN - 0194-911X
VL - 79
SP - 1091
EP - 1100
JO - Hypertension
JF - Hypertension
IS - 5
ER -