SUMMARY1. Sympathetic vasomotor nerves play a major role in determining the level of arterial blood pressure and the distribution of cardiac output. The present review will discuss briefly the central regulatory mechanisms that control the sympathetic outflow to the cardiovascular system in the short and long term.2. In the short term, the sympathetic vasomotor outflow is regulated by: (i) homeostatic feedback mechanisms, such as the baroreceptor or chemoreceptor reflexes; or (ii) feed-forward mechanisms that evoke cardiovascular changes as part of more complex behavioural responses.3. The essential central pathways that subserve the baroreceptor reflex and, to a lesser extent, other cardiovascular reflexes, have been identified by studies in both anaesthetized and conscious animals. A critical component of these pathways is a group of neurons in the rostral ventrolateral medulla that project directly to the spinal sympathetic outflow and that receive inputs from both peripheral receptors and higher centres in the brain. 4. Much less is known about the central pathways subserving feed-forward or 'central command' responses, such as the cardiovascular changes that occur during exercise or that are evoked by a threatening or alerting stimulus. However, recent evidence indicates that the dorsomedial hypothalamic nucleus is a critical component of the pathways mediating the cardiovascular response to an acute alerting stimulus.5. Long-term sustained changes in sympathetic vasomotor activity occur under both physiological conditions (e.g. a change in salt intake) and pathophysiological conditions (e.g. heart failure). There is evidence that the paraventricular nucleus in the hypothalamus is a critical component of the pathways mediating these changes.6. Understanding the central mechanisms involved in the long-term regulation of sympathetic activity and blood pressure is a major challenge for the future. As a working hypothesis, a model is presented of the postulated central mechanisms that result in sustained changes in sympathetic vasomotor activity that are evoked by different types of chronic stimulation.

Physiological and anatomic methods were used to determine whether neurons in the rostral ventrolateral medulla (RVLM), nucleus tractus solitarius (NTS), or hypothalamic paraventricular nucleus (PVN) mediate the cardiovascular response evoked from the dorsomedial hypothalamic nucleus (DMH), which is believed to play a key role in mediating responses to stress. In urethane-anesthetized rats, activation of neurons in the DMH by microinjection of bicuculline resulted in a large increase in arterial pressure, heart rate, and renal sympathetic nerve activity. The pressor and sympathoexcitatory responses, but not the tachycardic response, were greatly reduced after bilateral muscimol injections into the RVLM even when baseline arterial pressure was maintained at a constant level. These responses were not reduced by muscimol injections into the PVN or NTS. Retrograde tracing experiments identified many neurons in the DMH that projected directly to the RVLM. The results indicate that the vasomotor and cardiac components of the response evoked from the DMH are mediated by pathways that are dependent and independent, respectively, of neurons in the RVLM.

No abstract

Abstract-Leptin, a circulating hormone produced by adipose tissue, is believed to act on the hypothalamus to increase sympathetic vasomotor activity, in addition to its well-known effects on appetite and energy expenditure. In this study, we determined the cardiovascular effects of direct application of leptin to specific cell groups within the hypothalamus that are known to be activated by circulating leptin. In rats anesthetized with urethane, microinjections of leptin (16 ng in 20 nL solution) were made into the ventromedial hypothalamic nucleus, dorsomedial hypothalamic nucleus, and paraventricular nucleus. Compared with vehicle solution, microinjections of leptin into the ventromedial hypothalamic nucleus evoked significant increases in arterial pressure and renal sympathetic nerve activity, but not heart rate. In contrast, microinjections of leptin into the dorsomedial hypothalamic nucleus evoked significant increases in arterial pressure and heart rate but not renal sympathetic nerve activity, whereas microinjections of leptin into the paraventricular nucleus had no significant effect on any of the measured cardiovascular variables. These results indicate that the ventromedial and dorsomedial hypothalamic regions might be important sites at which leptin activation leads to increases in sympathetic vasomotor activity and heart rate, as occurs in obesity-related hypertension. (Hypertension. 2003;42:488-493.)Key Words: hypothalamus Ⅲ sympathetic nervous system Ⅲ arterial pressure Ⅲ heart rate Ⅲ brain Ⅲ hypertension, experimental Ⅲ obesity I t is well established that the circulating hormone leptin, which is produced mainly in white adipose tissue, contributes to body weight homeostasis by reducing appetite and increasing energy expenditure. 1,2 The increase in energy expenditure is due to activation of sympathetic nerves that innervate brown adipose tissue. 3 In addition to these effects, it has also been shown that intravenous administration of leptin increases the activity of sympathetic nerves that innervate the kidneys, hindlimb vasculature, and adrenal glands in anesthetized rats, 3 whereas long-term intravenous or intracarotid infusions of leptin increase arterial pressure and heart rate (HR) in conscious rats. 4 It has therefore been suggested that leptin-induced increases in the activity of sympathetic vasomotor and cardiac nerves might be an important component in obesityrelated hypertension. 5 The leptin-induced increases in sympathetic vasomotor activity, arterial pressure, and HR appear to be mediated via action on the brain, because short-term administration of leptin into the lateral ventricles increases arterial pressure in conscious rats. 6,7 Similarly, long-term administration of leptin into the lateral ventricles of conscious rats also results in a sustained increase in arterial pressure. 8 Circulating leptin has been shown to access the brain via a saturable transport system, 9,10 but the site(s) in the brain at which leptin acts to increase sympathetic vasomotor activity is unknown. Studi...

No abstract