Mineralocorticoid treatment upregulates the hypothalamic vasopressinergic system of spontaneously hypertensive rats

PIETRANERA, LUCIANA; SARAVIA, FLAVIA; ROIG, PAULINA; LIMA, ANALÍA; DE NICOLA, ALEJANDRO F.

NEUROENDOCRINOLOGY

Karger, AG

Año: 2004 vol. 80 p. 100 - 110

0028-3835

Mineralocorticoids 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 systolic blood pressure of 190 ± 5 mm Hg and normotensive WKY rats ( 130 ± 5 mm Hg ) were treated s.c. 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 arginine vasopressin (AVP) mRNA. In the basal state, SHR rats demonstrated higher number of AVP mRNA and V1aR immunopositive cells in the magnocellular division of the paraventricular hypothalamic nucleus (PVN) than WYK rats. After DOCA injection, SHR responded with a significant increase in both parameters respect of 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 and organum vasculossum of the lamina terminals (OVLT), a circumventricular region showing anatomical connections with the PVN. In vehicle injected rats, the PVN of SHR showed higher number of Fos-positive nuclei than WKY rats, whereas after DOCA treatment, a significant increment occurred in the OVLT but not the PVN 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.