Fig. 1.

Counter “clockwise” productivity to hypertension. Behavioral disorders such as sleep apnea, shift work, or inadequate sleep impair central clock function, which may affect the release of hormones such as melatonin (Mel), which then impinge on blood pressure-regulating organs (heart, kidney, vasculature). Similarly, diet or other disturbances that originate from aberrations peripheral to the central nervous system may modify circadian clock function (depicted as distortion in the components Bmal1, Per, Cry, and Clock along black arrow) in peripheral tissues that are extrinsic to the organs/tissues important in the pressor response. These extrinsic peripheral tissues such as liver or the adrenal gland may affect release of pressor-modifying mediators [liver/angiotensin-converting enzyme; adrenal/epinephrine (Epi)], which then impinge on the pressure-regulating tissues. There may also be direct peripheral clock dysfunction in tissues such as heart, kidney, and vasculature that are intrinsically critical in blood pressure regulation by modulating the expression of ion channels (αENAC), paracrine signals (nitric oxide/NO), and receptors (adrenergic receptor/AR). An additional level of complexity is that hypertension itself alters circadian clock function in peripheral tissues (red dashed arrow) to induce a feedforward spiral of dysfunction.