Greaney Jody L, Darling Ashley M, Mogle Jacqueline, Saunders Erika F H
Department of Kinesiology, The University of Texas at Arlington (J.L.G., A.M.D.).
Edna Bennett Pierce Prevention Research Center, The Pennsylvania State University, University Park, PA (J.M.).
Hypertension. 2022 May;79(5):1091-1100. doi: 10.1161/HYPERTENSIONAHA.122.18985. Epub 2022 Mar 2.
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.
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 to 10 mol/L) and, separately, during the perfusion of norepinephrine (10 to 10 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 to 10 mol/L).
Isoproterenol-induced vasodilation was blunted in adults with MDD (188.9±70.1 HA versus 128.3±39.4 au MDD, =0.025). Net norepinephrine-induced vasoconstriction was exaggerated in adults with MDD (-0.16±0.54 HA versus -0.75±0.56 au MDD, =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, <0.01) but had no effect in adults with MDD (-0.75±0.56 norepinephrine versus -1.58±1.56 au propranolol, =0.08).
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.
重度抑郁症（MDD）与交感神经过度活跃及外周肾上腺素能受体功能改变有关；然而，尚无研究直接评估成年MDD患者的血管收缩反应性。我们检验了以下假设：与健康非抑郁成年人（HA）相比，成年MDD患者中β-肾上腺素能受体介导的血管舒张功能会减弱，且在功能上会导致去甲肾上腺素诱导的血管收缩反应过度。
对13名HA（8名女性；24±4岁）和12名成年MDD患者（8名女性；22±3岁），在皮内微透析灌注β-肾上腺素能受体激动剂异丙肾上腺素（10至10 mol/L）期间测量红细胞通量，另外，在单独灌注去甲肾上腺素（10至10 mol/L）以及与β-肾上腺素能受体拮抗剂普萘洛尔（2 mmol/L）联合灌注期间测量红细胞通量。通过灌注血管紧张素II（10至10 mol/L）评估非肾上腺素能血管收缩。
成年MDD患者中异丙肾上腺素诱导的血管舒张功能减弱（HA为188.9±70.1，MDD为128.3±39.4 au，P = 0.025）。成年MDD患者中去甲肾上腺素诱导的净血管收缩反应过度（HA为-0.16±0.54，MDD为-0.75±0.56 au，P = 0.014）；然而，血管紧张素II诱导的血管收缩在两组间无差异。普萘洛尔增强了HA中去甲肾上腺素诱导的血管收缩（去甲肾上腺素为-0.16±0.54，普萘洛尔为-1.60±1.40 au，P<0.01），但对成年MDD患者无影响（去甲肾上腺素为-0.75±0.56，普萘洛尔为-1.58±1.56 au，P = 0.08）。
成年MDD患者中β-肾上腺素能受体介导的微血管舒张功能减弱，并导致肾上腺素能血管收缩反应过度。β-肾上腺素能受体介导的血管舒张的血管保护作用的相对丧失可能导致外周阻力增加，从而促使成年MDD患者发生高血压。
