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 - Funding Information:
We appreciate the effort expended by the volunteer participants. We also thank Jane Cloud, MS for her laboratory assistance. Graphical abstract created with BioRender.com. National Institutes of Health grants HL133414 and MH123928 (J.L. Greaney). J.L. Greaney and E.F.H. Saunders conceived and designed research; J.L. Greaney and A.M. Darling performed experiments; J.L. Greaney analyzed data; J.L. Greaney, A.M. Darling, J. Mogle, and E.F.H. Saunders interpreted results of experiments; J.L. Greaney prepared figures; J.L. Greaney drafted article; J.L. Greaney, A.M. Darling, J. Mogle, and E.F.H. Saunders edited and revised article; J.L. Greaney, A.M. Darling, JM, and E.F.H. Saunders approved final version of article.
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 -