Activation of 5-hydroxytryptamine 1A receptors suppresses the cardiovascular response evoked from the dorsomedial hypothalamic nucleus.

The dorsomedial hypothalamic nucleus is a key component of the central pathways subserving the cardiovascular response to psychological stress, which is believed to be an important risk factor for hypertension. Previous studies indicate that 5-hydroxytryptamine 1A receptors can modulate the cardiovascular responses associated with stress. In this study, we determined in anesthetized rats the effects of systemic or intracisternal administration of 8-hydroxy-2-(di-n-propylamino)tetralin, a selective agonist of 5-hydroxytryptamine 1A receptors, and then subsequent administration of the selective antagonist WAY-100635 on the cardiovascular response evoked by activation of the dorsomedial hypothalamic nucleus (by microinjection of bicuculline). The increase in mean arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) evoked by bicuculline injection into the dorsomedial hypothalamic nucleus was greatly reduced (by 80% to 90%) by administration of 8-hydroxy-2-(di-n-propylamino)tetralin and then completely restored by subsequent administration of WAY-100635, whether administered systemically or intracisternally. In contrast, systemic administration of 8-hydroxy-2-(di-n-propylamino)tetralin had no significant effect on the baseline level or reflex changes in RSNA evoked by chemoreceptor or baroreceptor stimulation and resulted in only a modest reduction (12 mm Hg) in baseline mean arterial pressure. The results indicate that activation of 5-hydroxytryptamine 1A receptors in the brain stem causes a potent and selective suppression of the hypertensive and sympathoexcitatory response evoked by stimulation of the dorsomedial hypothalamic nucleus but has little effect on the tonic level or baroreceptor or chemoreceptor reflex control of RSNA.

Mood change and immune status of human subjects in a 10-day confinement study.

INTRODUCTION: Stress is a known factor that causes changes in leukocyte distribution or depression in lymphocyte proliferation. We reported previously that a 10-d confinement caused changes in immune status. Here we report the relationship between mood changes and immune parameters in the subjects confined for 10-d. METHODS: There were 10 subjects (age 20-27 yr, mean 22.8 yr) who participated in a 10-d confinement study. They were divided into 2 groups with regard to their psychological aspects and their immune parameters were then compared. Blood samples were taken once before, three times during, and once after confinement. The percentages of granulocytes, natural killer (NK) cells, and cells positive for CD69, an early activation marker, were analyzed by flow cytometry. Face scale was employed to estimate subjects' mood. RESULTS: The group that showed an increase in mood scale toward the end of the confinement showed changes in all immune parameters. In contrast, less marked changes were seen in the group that showed no mood changes throughout the experiment. DISCUSSION: These results indicate that the observed immune changes were related to the mood changes, and that mood change seems to be one of the causes of the immunological changes seen in confined environments, such as in space stations or submarines. The percentages of NK cells, granulocytes, and CD69 expression may be useful criteria for detecting immunological deterioration caused by stress, or for selecting astronauts who are immunologically stable against the challenge of confinement stress.

Effects of 10-day confinement on the immune system and psychological aspects in humans.

We investigated the changes in percentages of leukocyte subpopulations, natural killer (NK) cells, CD69-expressing lymphocytes, and psychological aspects in 10 subjects who participated in a 10-day confinement study. Suppression of lymphocyte proliferative reaction and changes in leukocyte distribution are known to occur in space. These responses are similar to those induced by psychological stress. Ground-based confinement studies are suitable for validating the effects of stress arising only due to confinement. Two groups, consisting of five male subjects (ages 20-27 yr, mean 22.8 yr) each, participated in a 10-day confinement study. Blood samples were taken once before, three times during, and once after the confinement and activated with an anti-CD2 agonistic antibody cocktail. The percentages of leukocyte subpopulations, NK (CD45(+)CD56+) cells, and activated lymphocytes (CD45(+)CD69+) were measured by flow cytometric assay. The face scale test was used to measure psychological aspects. The percentage of CD69+ lymphocytes decreased during the period of confinement. This was mostly caused by changes in the ratio between NK and non-NK lymphocytes. The face scale showed that the subjects' moods improved toward the postconfinement period. Consistent with the face scale, the percentages of innate immune cells, such as NK cells and granulocytes, increased during the postconfinement period. We concluded that the changes in the distribution of immune cells caused by stress plays an important role in suppression of proliferative reactivity. The observed physiological reactions were specific to the confined environment, and the stress caused by confinement plays a role in the immune changes observed in space.

Effects of adrenaline and cortisone on the early activation of lymphocytes.

Using whole blood, we examined the effects of stress hormones on CD69 expression in Natural Killer (NK) cells. A series of diluted adrenaline or cortisone was added to 1 ml of whole blood. Propranolol was used to block the beta-adrenergic effect. The blood samples were activated with CD2/CD2R mitogenic antibody solution for four hours under 37 degrees C. Then CD69 antigen on NK cells was analyzed by flowcytometric assay. Adrenaline and cortisone doses dependently suppressed CD69 expression on NK cells. Propranolol blocked the suppressive effect of adrenaline. CD69 expression was significantly higher than the control when only propranolol was added. We concluded that blood constituents acting on mitogenic reaction and stress hormones affect the early stage on the way to proliferation and differentiation.