A HYPERADRENERGIC STATE IN HYPERTENSION IS ASSOCIATED WITH MOOD DISTURBANCE AND IMPAIRED STRESS-MODULATED VASOMOTOR RESPONSES

Abstract

Objective: Increasing evidence suggests a high prevalence of affective disorders in hypertension, however, the physiological associations remain unclear. Noradrenergic activation in the central and peripheral nervous systems is a putative mechanism that may explain the link between both conditions. Here, we investigate whether these stress-sensitive co-morbidities may be dependent on basal noradrenergic activity and whether vascular responses to centrally acting stimuli vary according to noradrenergic activity. Design and method: We examined the relation of affective disorders and stress-mediated vascular responses to plasma concentrations of normetanephrine (NMN), a measure of noradrenergic activity, in subjects with primary hypertension. Subjects on antidepressant medication, alpha- and beta-blockers were excluded. The Patient Health Questionnaire (PHQ-9), the 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDSSR-16), and Generalised Anxiety Disorder-7 (GAD-7) questionnaires were used for the evaluation of symptoms of depression and anxiety. Forearm blood flow (strain gauge plethysmography) was used to assess vascular responses to mental stress (Stroop colour-word test) and slow breathing (by biofeedback), interventions that respectively increase or decrease noradrenergic activity in the pre-frontal cortex and locus coeruleus. Results: 100 subjects (53% male) with (mean ± SD) age 43.4 ± 10.9 years were recruited. 88% of subjects were treated with anti-hypertensive medications and 4% had type 2 diabetes. 31% and 34% of the study population scored moderate to severe depression for PHQ-9 and QIDSSR-16 respectively indicating significant mood disturbance. Scores representing low mood and high anxiety were 2-3-fold higher for hypertensive subjects in the highest compared to lowest NMN tertiles (PHQ-9: 9.2 ± 5.8 vs 3.8 ± 2.7, P < 0.001; QIDSSR-16: 12.3 ± 4.9 vs 4.5 ± 3.5, P = 0.003; GAD-7: 9.0 ± 5.5 vs 4.6 ± 3.8, P = 0.003). Forearm vasodilator responses to mental stress and vasoconstrictor responses to slow breathing were attenuated in those with high compared to low NMN (28.3 ± 21% vs. 47.1 ± 30% increases for mental stress and 3.7 ± 21% vs. 18.6 ± 15% decreases for slow breathing for highest vs. lowest tertiles of NMN, both P < 0.01). Conclusions: A hyperadrenergic state in hypertension is associated with mood disturbance and impaired stress-modulated vasomotor responses. This association may be mediated by chronic stress impinging on pathways regulating central arousal and peripheral sympathetic nerve activity.