Relationships between behavioral rhythms, plasma corticosterone and hypothalamic circadian rhythms.

Circadian rhythms in physiological processes and behaviors were compared with hypothalamic circadian rhythms in norepinephrine (NE) metabolites, adrenergic transmitter receptors, cAMP, cGMP and suprachiasmatic nucleus (SCN) arginine vasopressin (AVP) in a single population of rats under D:D conditions. Eating, drinking and locomotor activity were high during the subjective night (the time when lights were out in L:D) and low during the subjective day (the time when lights were on in L:D). Plasma corticosterone concentration rose at subjective dusk and remained high until subjective dawn. Binding to hypothalamic alpha 1- and beta-adrenergic receptors also peaked during the subjective night. Cyclic cGMP concentration was elevated throughout the 24-hr period except for a trough at dusk, whereas DHPG concentration peaked at dawn. Arginine vasopressin levels in the suprachiasmatic nucleus peaked in the middle of the day. No rhythm was found either in binding to the alpha 2-adrenergic receptor, or in MHPG or cAMP concentration. Behavioral and corticosterone rhythms, therefore, are parallel to rhythms in hypothalamic alpha 1- and beta-receptor binding and NE-release. Cyclic GMP falls only at dusk, suggesting the possibility that cGMP inhibits activity much of the day and that at dusk the inhibition of nocturnal activity is removed. SCN AVP, on the other hand, peaking at 1400 hr, may play a role in the pacemaking function of the SCN that drives these other rhythms.

Changes in the vasopressin content of discrete brain regions in response to stimuli for vasopressin secretion.

In order to better understand the function of vasopressin-containing axons which project to areas outside the hypothalamus, we measured vasopressin content in hypothalamic and extrahypothalamic brain regions following various periods of oral hypertonic saline or 1 week after pituitary stalk section. The supraoptic and paraventricular nuclei and nearly all of the brain regions examined which are known to receive vasopressin-containing axons from these nuclei showed parallel changes in vasopressin levels in response to both stimuli. In response to hypertonic saline there was an initial rise followed by a fall in vasopressin content. The suprachiasmatic and lateral septal nuclei, as well as the nucleus of the solitary tract, were unaffected by either stimulus. These results indicate that there are at least two functionally different vasopressin systems within the central nervous system, one of which is responsive to osmotic stimulation.

Anteroventral hypothalamus and hemorrhagic shock: cardiovascular and neuroendocrine responses.

The anteroventral third ventricle (AV3V) region was shown to be a site of central integration of sympathetic pressor pathways and central pressor and vasopressin (VP) release by angiotensin II (ANG II). Since the AV3V area seems to have an important role in the regulation of the three major pressor systems, we investigated the role of the AV3V in cardiovascular recovery after hemorrhage, a known stimulus for sympathetic, ANG II, and VP release. Conscious AV3V-lesioned (n = 19) and sham-operated rats (n = 14) underwent bleeding (40% of blood volume) through an arterial line. Mean blood pressure, heart rate, and plasma ANG II, VP, and catecholamines were monitored over 24 h. The exact site of lesion was determined by microscopic examination. The mean blood pressure and heart rate of both groups of rats were not different before or after hemorrhage. Plasma catecholamines, ANG II, and VP responses were also the same as were hematocrit and water consumption 24 h after the bleeding. Despite the lack of difference between control and lesioned animals with regard to cardiovascular, humoral, and neuroendocrine responses to hypovolemia, the AV3V-lesioned rats had a significantly higher early mortality rate. These data indicate that the AV3V may be an important region in recuperation and survival after hemorrhagic shock, but through mechanisms unrelated to activation of VP, renin-ANG II, or the sympathetic nervous system.

Central cardiovascular effects of vasotocin, oxytocin and vasopressin in conscious rats.

Arg8-vasotocin (AVT), oxytocin and Arg8-vasopressin (AVP) were injected into the i.c.v. space and/or the hypothalamus of awake, freely moving rats in order to investigate the potential role of these neuropeptides in central cardiovascular control. AVT (0.015-10 nmol) injected i.c.v. caused dose-dependent pressor responses; low doses also elicited tachycardia, whereas the higher doses (1 and 10 nmol) produced bradycardia. In contrast, oxytocin injections into the lateral ventricle (0.015-100 nmol) had no significant cardiovascular effects. Plasma vasopressin was not affected by i.c.v. administration of oxytocin or AVT except at the highest dose of AVT. AVT (0.1 or 1 nmol) and AVP (0.015 or 0.1 nmol) injected into the hypothalamic nucleus preopticus medialis (POM) increased blood pressure and heart rate; these changes were much greater than with comparable doses of AVT injected i.c.v. Plasma levels of norepinephrine and epinephrine, but not vasopressin, were significantly elevated during the pressor period induced by 1 nmol of AVT injected into the POM. The pressor and cardiac accelerating effects of AVT (1 nmol) injected into the POM were significantly diminished in bilaterally adrenal demedullated, bretylium-treated rats. These data suggest a role for AVT, but not oxytocin, in central cardiovascular control through activation of the sympathoadrenomedullary axis. The anteroventral hypothalamus might play a central role in these autonomic effects of vasotocin. It is also suggested that AVP and AVT share some central autonomic effects due to similarities in the side-chain of their molecules.

Catecholamines and vasopressin in forebrain nuclei of hypertension prone and resistant rats.

Catecholamine and vasopressin content were studied in discrete brain nuclei of the Sabra strain of hypertension prone (SBH) and resistant (SBN) rats. Higher concentrations of dopamine, norepinephrine and epinephrine were observed in the median eminence of SBN compared to SBH or controls (SB) rats. Dopamine and epinephrine levels were higher in the lateral septal nucleus of SBH rats as compared to SBN or SB. Vasopressin content in discrete regions along the hypothalamo-pituitary axis was elevated in both SBH and SBN as compared to SB, but were especially elevated in the SBH group. The catecholamine and vasopressin changes found in SBH are different than those described in other genetically hypertensive rats indicating a difference in either the pathogenesis or central response to hypertension of this strain.