A hyperadrenergic state in hypertension is associated with depressive symptoms and impaired stress-modulated vasomotor responses: evidence for chronic stress as a common aetiology for a hypertension/depression phenotype.

Abstract

Background: Noradrenergic activation in the central and peripheral nervous systems is a putative mechanism explaining the link between hypertension and affective disorders.

Aims: We investigated whether these stress-sensitive comorbidities may be dependent on basal noradrenergic activity and whether vascular responses to centrally acting stimuli vary according to noradrenergic activity.

Method: We examined the relation of affective disorders and stress-mediated vascular responses to plasma concentrations of normetanephrine, a measure of noradrenergic activity, in subjects with primary hypertension (n = 100, mean ± s.d. age 43 ± 11 years, 54% male). The questionnaires Patient Health Questionnaire-9 (PHQ-9), 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDSSR-16) and Generalized Anxiety Disorder-7 (GAD-7) were used for evaluation of symptoms of depression and anxiety. Forearm blood flow (strain gauge plethysmography) was used to assess vascular responses to mental stress and to device-guided breathing (DGB), interventions that respectively increase or decrease noradrenergic activity in the prefrontal cortex and locus coeruleus.

Results: Low mood and high anxiety were two- to threefold higher for hypertensive subjects in the highest compared with the lowest normetanephrine tertiles (each P < 0.005). Forearm vasodilator responses to mental stress and vasoconstrictor responses to DGB were attenuated in those with high compared with low normetanephrine (28.3 ± 21% v. 47.1 ± 30% increases for mental stress and 3.7 ± 21% v. 18.6 ± 15% decreases for DGB for highest versus lowest tertiles of normetanephrine, each 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.