Mineralocorticoid Pretreatment Enhances Angiontensin II‐Induced Neuronal Excitation But Not Salt Drinking in Male Fischer Rats

Abstract

Central administration of angiotensin (Ang) II stimulates thirst and sodium intake via the AT-1 receptor. Mineralocorticoid pretreatment enhances Ang II-induced drinking of hypertonic salt solutions (i.e. the synergy theory) in Wistar and Sprague-Dawley rats. Electrophysiological experiments using iontophoretic application of Ang II, and the AT-1 receptor specific nonpeptide antagonist losartan, have shown excitation of neurones in the preoptic/medial septum region of urethane anaesthetised male Wistar rats. Deoxycorticosterone acetate (DOCA) pretreatment further enhanced this neuronal excitation to Ang II and reduced the responses to losartan. This generated the hypothesis that DOCA-enhanced Ang II-induced neuronal excitation was necessary for the enhanced salt intake of synergy theory. We tested this hypothesis in Fischer 344 rats that are known to have a low basal salt appetite and reduced sensitivity for i.c.v. Ang II. We compared the effect of DOCA pretreatment on i.c.v. Ang II-induced water and 2% NaCl intake in behaving adult male, Fischer rats, as well as preoptic/medial septum region neuronal responses to Ang II and losartan, using a seven-barrelled micro-iontophoretic electrode sealed to a recording electrode in urethane anaesthetised, male Fischer rats. Two groups were used: one pretreated with DOCA (0.5 mg/day for 3 days) and the other comprising controls, treated with isotonic saline. Ang II applied iontophoretically increased activity in 31% of the spontaneously active neurones. Following DOCA pretreatment, the responsiveness to Ang II (when applied after aldosterone) was increased. By contrast, in the behaving animals, water and 2% NaCl intake in response to i.c.v. Ang II were not enhanced by DOCA pretreatment. These results do not support the working hypothesis but could be interpreted as evidence for the existence of two separately modulated central Ang II systems: one responding to mineralocorticoids with increased neuronal activity and the other responsible for the Ang II-induced sodium appetite in conscious rats.

Central interactions of aldosterone and angiotensin II in aldosterone- and angiotensin II-induced hypertension

“…Numerous in vitro and in vivo studies have demonstrated a direct role of Aldo in the development of cardiovascular disease via oxidative stress (11,36,43,48). Long-term administration of an NADPH oxidase inhibitor, apocynin, in the drinking water to deoxycorticosterone acetate (DOCA)-salt rats significantly decreased systolic BP and superoxide production in aortic rings compared with that of rats treated with DOCA-salt alone (1).…”

“…Recently, it has been shown that Aldo significantly increased the number and expression of AT 1 Rs and ACEs in the brain (63,64). Mineralocorticoid pretreatment can enhance ANG IIinduced neuronal excitation in the preoptic/medial septum region (36). However, there have been few studies investigating the central interactions between ANG II and Aldo.…”

Mineralocorticoid modulation of central angiotensin-induced neuronal activity, water intake and sodium appetite

“…In a subsequent study on Fischer rats, again looking at behavior of both the intact, non-anesthetized animal and neurons in the forebrain of anesthetized animals, it was observed that DOCA pretreatment could increase the responsiveness of forebrain neurons to AngII, as reported previously in Wistar rats, but that the salt drinking responses to centrally applied AngII were not enhanced (23). Thus, the two phenomena can be separated and perhaps enhancement can be observed depending on the degree of increased excitability, or degree of decreased inhibition, of the forebrain neurons.…”