Elevated corticosterone in the dorsal hindbrain increases plasma norepinephrine and neuropeptide Y, and recruits a vasopressin response to stress

Abstract

Repeated stress and chronically elevated glucocorticoids cause exaggerated cardiovascular responses to novel stress, elevations in baseline blood pressure, and increased risk for cardiovascular disease. We hypothesized that elevated corticosterone (Cort) within the dorsal hindbrain (DHB) would: 1) enhance arterial pressure and neuroendocrine responses to novel and repeated restraint stress, 2) increase c-Fos expression in regions of the brain involved in sympathetic stimulation during stress, and 3) recruit a vasopressin-mediated blood pressure response to acute stress. Small pellets made of 10% Cort were implanted on the surface of the DHB in male Sprague-Dawley rats. Blood pressure was measured by radiotelemetry. Cort concentration was increased in the DHB in Cort-treated compared with Sham-treated rats (60 ± 15 vs. 14 ± 2 ng Cort/g of tissue, P < 0.05). DHB Cort significantly increased the integrated arterial pressure response to 60 min of restraint stress on days 6, 13, and 14 following pellet implantation (e.g., 731 ± 170 vs. 1,204 ± 68 mmHg/60 min in Sham- vs. Cort-treated rats, day 6, P < 0.05). Cort also increased baseline blood pressure by day 15 (99 ± 2 vs. 108 ± 3 mmHg for Sham- vs. Cort-treated rats, P < 0.05) and elevated baseline plasma norepinephrine and neuropeptide Y concentrations. Cort significantly enhanced stress-induced c-Fos expression in vasopressin-expressing neurons in the paraventricular nucleus of the hypothalamus, and blockade of peripheral vasopressin V1 receptors attenuated the effect of DHB Cort to enhance the blood pressure response to restraint. These data indicate that glucocorticoids act within the DHB to produce some of the adverse cardiovascular consequences of chronic stress, in part, by a peripheral vasopressin-dependent mechanism.

Divergent regulation of distinct glucocorticoid systems in alcohol dependence

“…For example, it is noteworthy that in addition to CRF, the role of GR in the modulation of vasopressin gene expression and function may explain some of the effects of glucocorticoid dysregulation on stress responsiveness and alcohol dependence (Daubert, Looney, Clifton, Cho, & Scheuer, 2014; Kim, Summer, Wood, & Schrier, 2001; Rabadan-Diehl & Aguilera, 1998; Zhou & Kreek, 2014). Along with CRF, vasopressin is present in parvocellular PVN neurons and acts as a co-regulator of the HPA axis (Sawchenko, Swanson, & Vale, 1984; Whitnall, Mezey, & Gainer, 1985) through its actions on V1b receptors.…”

The effects of melatonin on the activity of the c-fos gene in the structures of the hypothalamic paraventricular nucleus under prolonged lighting

“…As is known, these structures have complex cellular organization and include magnocellular and parvicellular subnuclei, whose neurons differ not only in size and efferent innervation but also in the spectrum of synthesized neuropeptides (Flak et al, 2014;Fan et al, 2016;Franco et al, 2016, Chun et al, 2017. These features determine the important role of PVN not only in the endocrine regulation of the trophic functions of the adenohypophysis, but also in the realization of the neuroendocrine response of the body to stress of various genesis, including prolonged illumination (Daubert et al, 2014;Herman et al, 2016;Miyake et al, 2016;Ordyan et al, 2016).…”

Novel mechanism within the paraventricular nucleus reduces both blood pressure and hypothalamic pituitary-adrenal axis responses to acute stress

“…Radiotelemetry transmitters (model PA-C40; Data Sciences International, St. Paul, MN) were implanted into the descending aorta under isoflurane anesthesia for the measurement of blood pressure and heart rate as previously described (13). The abdominal aorta was isolated from a midline incision and briefly occluded, and the tip of the catheter was inserted using a 21-gauge needle.…”

“…On the day of an experiment, the catheter was attached to a piece of sterile extension tubing so that samples could be obtained without touching the animal, as previously described (13). The rats remained in their home cages and at least 2 h elapsed from the time the extension tubing was attached to the withdrawal of the first blood sample.…”

“…Plasma corticosterone concentration was measured in duplicate using double antibody I 125 radioimmunoassay kits purchased from MP Biomedicals (Solon, OH) as previously described (13,52).…”