Long-term mineralocorticoid-induced changes in rat neuron properties plus interaction of aldosterone and ANG II.
The central site of action and the neuronal mechanism of the robust sodium appetite initiated in rats by the synergistic action of a peripheral priming with mineralocorticoid [deoxycorticosterone acetate (DOCA)] and subsequent central angiotensin II (ANG II) were investigated using iontophoretic and electrophysiological techniques in urethan-anesthetized, DOCA-pretreated (0.5 mg/day sc for 3 days) or nonpretreated male Wistar rats. A significantly greater number of spontaneously active neurons were recorded in the medial septum and median preoptic area, but not in the cortex, in rats pretreated with DOCA than found in the nonpretreated animals (9.3 +/- 1.2 per electrode descent; n = 19 vs. 6.1 +/- 0.7 per descent; n = 21; P < 0.001). The firing rate of the spontaneously active neurons was also significantly increased in the DOCA-pretreated animals. A greatly increased neuronal sensitivity (increased activity lasting up to 10 min after the end of the application) to iontophoretically applied ANG II was found in 32% of the ANG II-sensitive neurons in pretreated animals. This prolonged response was never observed in the nonpretreated animals. Iontophoretically applied aldosterone produces rapid neuronal excitation in both groups of rats and renders previously insensitive neurons sensitive to iontophoretically applied ANG II only in the DOCA-pretreated animals. This forebrain region, therefore, contains neurons that undergo a mineralocorticoid pretreatment-induced and/or a rapid aldosterone-induced sensitization to ANG II, which may be the neuronal mechanism whereby a persistent sodium appetite, induced by the synergistic action of these two hormones, is stimulated.
Thornton
S N
SN
Centre National de la Recherche Scientifique, Unité de Recherche Associée 637, Collège de France, Paris.
Nicolaïdis
S
S
D000450:Aldosterone / Q000008:administration & dosage / Q000494:pharmacology*; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D003900:Desoxycorticosterone / Q000008:administration & dosage / Q000494:pharmacology*; D007478:Iontophoresis; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011301:Preoptic Area / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000804:Angiotensin II; D001127:Arginine Vasopressin; D003900:Desoxycorticosterone; D000450:Aldosterone; D009320:Atrial Natriuretic Factor