Mineralocorticoid Treatment Upregulates the Hypothalamic Vasopressinergic System of Spontaneously Hypertensive Rats

Abstract

Mineralocorticoid effects in the brain include the control of cardiovascular functions, induction of salt appetite, interaction with the vasoactive neuropeptides arginine vasopressin (AVP) and angiotensin II and development or aggravation of hypertension. In this regard, mineralocorticoids may play a pathogenic role in rats with a genetic form of hypertension (spontaneously hypertensive rats, SHR). Our objective was to compare the response of the hypothalamic vasopressinergic system to mineralocorticoid administration in SHR and control Wistar-Kyoto (WKY) rats. Sixteen-week-old male SHR showing a systolic blood pressure of 190 ± 5 mm Hg and normotensive WKY rats (130 ± 5 mm Hg) were treated subcutaneously with oil vehicle or a single 10-mg dose of deoxycorticosterone acetate (DOCA). After 2 h, rats were sacrificed and brains prepared for immunocytochemistry of Fos and vasopressin V1a receptor (V1aR) and for non-isotopic in situ hybridization of AVP mRNA. In the basal state, SHR demonstrated a higher number of AVP mRNA- and V1aR-immunopositive cells in the magnocellular division of the paraventricular hypothalamic nucleus (PVN) than WKY rats. After DOCA injection, SHR responded with a significant increase in both parameters with respect to vehicle-injected SHR. In WKY rats, DOCA was without effect on AVP mRNA although it increased the number of V1aR-positive cells. Changes in the number of Fos-positive nuclei were measured in the PVN, median preoptic nucleus (MnPO) and organum vasculosum of the lamina terminalis (OVLT), a circumventricular region showing anatomical connections with the PVN. In vehicle-injected rats, the PVN of SHR showed a higher number of Fos-positive nuclei than in WKY rats, whereas after DOCA treatment, a significant increment occurred in the OVLT but not in the PVN or MnPO of the SHR group only. These data suggest that the enhanced response of the vasopressinergic system to mineralocorticoids may contribute to the abnormal blood pressure of SHR.

Vasopressin and Its Immune Effects in Septic Shock

“…The effects of corticosteroids on vasopressin levels and efficacy are consistent with studies showing that corticosteroids increase vasopressin mRNA [108] and restore responsiveness to vasopressin [109] .…”

SGK1 as a determinant of kidney function and salt intake in response to mineralocorticoid excess

“…In vitro experiments have indeed demonstrated the ability of SGK1 to upregulate the Na ϩ -K ϩ -ATPase (24,48,61,62). Mineralocorticoids have further been shown to upregulate Fos (41,42), angiotensin receptors (51), oxytocin receptors (51), vasopressin (20), and the vasopressin V 1a receptor (41,42). Vasopressin (11) and angiotensin II (9,29,45,50,51) in turn stimulate, whereas oxytocin (53) inhibits, salt intake.…”

Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances

“…75,76 In animal experiments, AVPR1A immunoreactive cells in the PVN increased after mineralocorticoid administration 77 and an AVPR1A antagonist resulted in a decrease in anxiety/depression-related behavior. 25 The increased AVPR1A mRNA found in the PVN of depressed patients may therefore be directly related with the symptoms of depression.…”