Felix Kreier

Short Sleep Duration as a Risk Factor for Hypertension Analyses of the First National Health and Nutrition Examination Survey

Depriving healthy subjects of sleep has been shown to acutely increase blood pressure and sympathetic nervous system activity. Prolonged short sleep durations could lead to hypertension through extended exposure to raised 24-hour blood pressure and heart rate, elevated sympathetic nervous system activity, and increased salt retention. Such forces could lead to structural adaptations and the entrainment of the cardiovascular system to operate at an elevated pressure equilibrium. Sleep disorders are associated with cardiovascular disease, but we are not aware of any published prospective population studies that have shown a link between short sleep duration and the incidence of hypertension in subjects without apparent sleep disorders. We assessed whether short sleep duration would increase the risk for hypertension incidence by conducting longitudinal analyses of the first National Health and Nutrition Examination Survey (n=4810) using Cox proportional hazards models and controlling for covariates. Hypertension incidence (n=647) was determined by physician diagnosis, hospital record, or cause of death over the 8- to 10-year follow-up period between 1982 and 1992. Sleep durations of ≤5 hours per night were associated with a significantly increased risk of hypertension (hazard ratio, 2.10; 95% CI, 1.58 to 2.79) in subjects between the ages of 32 and 59 years, and controlling for the potential confounding variables only partially attenuated this relationship. The increased risk continued to be significant after controlling for obesity and diabetes, which was consistent with the hypothesis that these variables would act as partial mediators. Short sleep duration could, therefore, be a significant risk factor for hypertension.

Selective parasympathetic innervation of subcutaneous and intra-abdominal fat — functional implications

The wealth of clinical epidemiological data on the association between intra-abdominal fat accumulation and morbidity sharply contrasts with the paucity of knowledge about the determinants of fat distribution, which cannot be explained merely in terms of humoral factors. If it comes to neuronal control, until now, adipose tissue was reported to be innervated by the sympathetic nervous system only, known for its catabolic effect. We hypothesized the presence of a parasympathetic input stimulating anabolic processes in adipose tissue. Intra-abdominal fat pads in rats were first sympathetically denervated and then injected with the retrograde transneuronal tracer pseudorabies virus (PRV). The resulting labeling of PRV in the vagal motor nuclei of the brain stem reveals that adipose tissue receives vagal input. Next, we assessed the physiological impact of these findings by combining a fat pad-specific vagotomy with a hyperinsulinemic euglycemic clamp and RT-PCR analysis. Insulin-mediated glucose and FFA uptake were reduced by 33% and 36%, respectively, whereas the activity of the catabolic enzyme hormone-sensitive lipase increased by 51%. Moreover, expression of resistin and leptin mRNA decreased, whereas adiponectin mRNA did not change. All these data indicate an anabolic role for the vagal input to adipose tissue. Finally, we demonstrate somatotopy within the central part of the autonomic nervous system, as intra-abdominal and subcutaneous fat pads appeared to be innervated by separate sympathetic and parasympathetic motor neurons. In conclusion, parasympathetic input to adipose tissue clearly modulates its insulin sensitivity and glucose and FFA metabolism in an anabolic way. The implications of these findings for the (patho)physiology of fat distribution are discussed.

SCN outputs and the hypothalamic balance of life

The circadian clock in the suprachiasmatic nucleus (SCN) is composed of thousands of oscillator neurons, each dependent on the cell-autonomous action of a defined set of circadian clock genes. Still, the major question remains how these individual oscillators are organized into a biological clock producing a coherent output able to time all the different daily changes in behavior and physiology. In the present review, the authors discuss the anatomical connections and neurotransmitters used by the SCN to control the daily rhythms in hormone release. The efferent SCN projections mainly target neurons in the medial hypothalamus surrounding the SCN. The activity of these preautonomic and neuroendocrine target neurons is controlled by differentially timed waves of, among others, vasopressin, GABA, and glutamate release from SCN terminals. Together, the data on the SCN control of neuroendocrine rhythms provide clear evidence not only that the SCN consists of phenotypically (i.e., according to neurotransmitter content) different subpopulations of neurons but also that subpopulations should be distinguished (within phenotypically similar groups of neurons) based on the acrophase of their (electrical) activity. Moreover, the specialization of the SCN may go as far as a single body structure, that is, the SCN seems to contain neurons that specifically target the liver, pineal, and adrenal.

Organization of circadian functions: interaction with the body.

The hypothalamus integrates information from the brain and the body; this activity is essential for survival of the individual (adaptation to the environment) and the species (reproduction). As a result, countless functions are regulated by neuroendocrine and autonomic hypothalamic processes in concert with the appropriate behaviour that is mediated by neuronal influences on other brain areas. In the current chapter attention will be focussed on fundamental hypothalamic systems that control metabolism, circulation and the immune system. Herein a system is defined as a physiological and anatomical functional unit, responsible for the organisation of one of these functions. Interestingly probably because these systems are essential for survival, their function is highly dependent on each others performance and often shares same hypothalamic structures. The functioning of these systems is strongly influenced by (environmental) factors such as the time of the day, stress and sensory autonomic feedback and by circulating hormones. In order to get insight in the mechanisms of hypothalamic integration we have focussed on the influence of the biological clock; the suprachiasmatic nucleus (SCN) on processes that are organized by and in the hypothalamus. The SCN imposes its rhythm onto the body via three different routes of communication: 1.Via the secretion of hormones; 2. via the parasympathetic and 3.via the sympathetic autonomous nervous system. The SCN uses separate connections via either the sympathetic or via the parasympathetic system not only to prepare the body for the coming change in activity cycle but also to prepare the body and its organs for the hormones that are associated with such change. Up till now relatively little attention has been given to the question how peripheral information might be transmitted back to the SCN. Apart from light and melatonin little is known about other systems from the periphery that may provide information to the SCN. In this chapter attention will be paid to e.g. the role of the circumventricular organs in passing info to the SCN. Herein especially the role of the arcuate nucleus (ARC) will be highlighted. The ARC is crucial in the maintenance of energy homeostasis as an integrator of long- and short-term hunger and satiety signals. Receptors for metabolic hormones like insulin, leptin and ghrelin allow the ARC to sense information from the periphery and signal it to the central nervous system. Neuroanatomical tracing studies using injections of a retrograde and anterograde tracer into the ARC and SCN showed a reciprocal connection between the ARC and the SCN which is used to transmit feeding related signals to the SCN. The implications of multiple inputs and outputs of the SCN to the body will be discussed in relation with metabolic functions.

The Metabolic Syndrome: A Brain Disease?

The incidence of obesity with, as consequence, a rise in associated diseases such as diabetes, hypertension and dyslipidemia − the metabolic syndrome − is reaching epidemic proportions in industrialized countries. Here, we provide a hypothesis that the biological clock which normally prepares us each morning for the coming activity period is altered due to a modern life style of low activity during the day and late‐night food intake. Furthermore, we review the anatomical evidence supporting the proposal that an unbalanced autonomic nervous system output may lead to the simultaneous occurrence of diabetes type 2, dyslipidemia, hypertension and visceral obesity.