The biological clock, the suprachiasmatic nucleus (SCN), is essential for our daily well-being. It prepares us for the upcoming period of activity by an anticipatory rise in heart rate, glucose and cortisol. At the same time the 'hormone of the darkness', melatonin, decreases. Thus, the time-ofday message penetrates into all tissues, interestingly not only by means of hormones but also by a direct neuronal influence of the SCN on the organs of the body. The axis between the SCN and the paraventricular nucleus of the hypothalamus (PVN) is crucial for the organization/ synchronization of the neuroendocrine and autonomic nervous system with the time of day. This SCNneuroendocrine PVN axis takes care of a timely hormonal secretion. At the same time, the SCN-autonomic PVN axis fine-tunes the organs by means of the autonomic nervous system for the reception of these hormones. Finally, the similar organization of the projections of the human SCN as compared with that in the rodent brain suggests that these basic principles of neuroendocrine autonomic interaction may also be true in the human. The physiological data collected in humans thus far seem to support this hypothesis, while pathological changes in the SCN of humans suffering from depression or hypertension indicate a role for the SCN in the etiology of these diseases.

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By using quantitative immunohistochemical and in situ hybridization techniques, we studied corticotropin-releasing hormone (CRH) -producing neurons of the hypothalamic paraventricular nucleus (PVN) in patients who suffered from primary hypertension and died due to acute cardiac failure. The control group consisted of individuals who had normal blood pressure and died of acute heart failure due to mechanical trauma. Both magno- and parvocellular populations of CRH neurons appeared to be more numerous in the PVN of hypertensive patients. Quantitative analysis showed approximately a twofold increase in the total number of CRH neurons and a more than fivefold increase in the amount of CRH mRNA in the hypertensive PVN compared with the control. It is suggested that synthesis of CRH in hypertensive PVN is enhanced. Increased activity of CRH-producing neurons in the PVN of hypertensive patients is proposed not only to entail hyperactivity of the hypothalamo-pituitary-adrenal axis, but also of the sympathetic nervous system and, thus, to be involved in the pathogenesis of hypertension.