Increased expression of magnocellular vasopressin mRNA in rats with deoxycorticosterone-acetate induced salt appetite.
The neuropeptides arginine vasopressin (AVP) and oxytocin (OT) have been implicated in the genesis of hypertension due to deoxycorticosterone acetate (DOCA)-salt treatment of uninephrectomized rats. In this work, we studied if DOCA treatment of intact rats in doses arousing a salt appetite (a prehypertensive state), modulated mRNA for AVP and OT in the hypothalamus. Male Sprague-Dawley rats were offered both tap water and 3% NaCl in separate bottles and received vehicle or subcutaneous injections of 10 mg DOCA on alternate days for 7 days (4 injections) or 17 days (9 injections). They developed a preference for 3% NaCl solutions 24-48 h after treatment. Brain slices from rats killed on the 8th or 18th day were exposed to 35S-labeled probes encoding prepro-AVP mRNA or OT mRNA, respectively. Expression of these mRNAs was measured in the magnocellular and parvocellular divisions of the paraventricular nucleus (PVN) and magnocellular cells of the supraoptic nucleus (SON). No changes were obtained in neuropeptide mRNA levels in the parvocellular division of the PVN between control and the two groups of DOCA-treated rats. However, DOCA-treated animals presented an increased number of grains per cell for AVP mRNA in the magnocellular division of the PVN and in magnocellular cells of the SON, as shown by group mean comparisons and frequency histograms. No changes were detected for OT mRNA. In a second series of studies, control or DOCA-treated rats were offered 3% NaCl or water as the only choice. Animals drinking 3% NaCl showed increased AVP and OT mRNA levels, whether they received DOCA or not. However, AVP mRNA levels in both nuclei were higher in DOCA-treated rats drinking 3% NaCl than in controls drinking salt solution. In comparison, control and DOCA-treated rats drinking water showed lower levels of AVP mRNA. OT mRNA levels in the SON remained unchanged in the same groups. The results suggest that in the magnocellular cells of the PVN and SON, increments in AVP mRNA are obtained following increments in salt intake produced by either mineralocorticoid treatment or exclusive salt drinking. In rats offered salt solution and water to drink, DOCA effects on AVP mRNA developed before changes occurred in serum sodium levels. Because combined DOCA + salt treatment induced a higher response in terms of AVP mRNA expression, we suggest that AVP could be a target of the central effects of the mineralocorticoid.
Grillo
C A
CA
Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, University of Buenos Aires, Argentina.
Saravia
F
F
Ferrini
M
M
Piroli
G
G
Roig
P
P
García
S I
SI
de Kloet
E R
ER
De Nicola
A F
AF
D000311:Adrenal Glands / Q000502:physiology; D000818:Animals; D001066:Appetite / Q000187:drug effects*; D001127:Arginine Vasopressin / Q000235:genetics*; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004326:Drinking / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology; D017403:In Situ Hybridization; D008297:Male; D009994:Osmolar Concentration; D010121:Oxytocin / Q000235:genetics; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology*; D013495:Supraoptic Nucleus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
D012333:RNA, Messenger; D001127:Arginine Vasopressin; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D010121:Oxytocin