Effect of chronic oral administration of a low dose of captopril on sodium appetite of hypothyroid rats: Influence of aldosterone treatment

Abstract

Rats rendered hypothyroid by treatment with methimazole develop an exaggerated sodium appetite. We investigated here the capacity of hypothyroid rats (N = 12 for each group) to respond to a low dose of captopril added to the ration, a paradigm which induces an increase in angiotensin II synthesis in cerebral areas that regulate sodium appetite by increasing the availability of circulating angiotensin I. In addition, we determined the influence of aldosterone in hypothyroid rats during the expression of spontaneous sodium appetite and after captopril treatment. Captopril significantly increased (P<0.05) the daily intake of 1.8% NaCl (in ml/100 g body weight) in hypothyroid rats after 36 days of methimazole administration (day 36: 9.2 ± 0.7 vs day 32: 2.8 ± 0.6 ml, on the 4th day after captopril treatment). After the discontinuation of captopril treatment, daily 1.8% NaCl intake reached values ranging from 10.0 ± 0.9 to 13.9 ± 1.0 ml, 48 to 60 days after treatment with methimazole. Aldosterone treatment significantly reduced (P<0.05) saline intake before (7.3 ± 1.6 vs day 0, 14.4 ± 1.3 ml) and after captopril treatment. Our results demonstrate that, although hypothyroid rats develop a deficiency in the production of all components of the renin-angiotensin-aldosterone system, their capacity to synthesize angiotensin II at the cerebral level is preserved. The partial reversal of daily 1.8% NaCl intake during aldosterone treatment suggests that sodium retention reduces both spontaneous and captopril-induced salt appetite. Key wordsPrevious studies have shown a reduction in NaCl aversion in hypothyroid rats with urinary sodium loss and an increase in sodium appetite in different experimental models (1-4). However, controversies still exist regarding the physiological mechanism responsible for sodium appetite, since genetic expression, synthesis and release of the components of the renin-angiotensin-aldosterone system are reduced in hypothyroidism (3,(5)(6)(7)(8)(9). Moreover, angiotensin II receptor density is altered in hypothyroidism. An increase in

Effect of Brain Serotoninergic Stimulation on Sodium Appetite of Euthyroid and Hypothyroid Rats

“…Analysis of the present data as a whole suggests that the sodium appetite attributed to deficient activity of the renin-angiotensin-aldosterone system and to a presumable increase in the expression of AT1 receptors implied in this homeostatic behaviour (Fregly & Rowland, 1985;Belló & Covian, 1991;Ventura et al 2001;Badauê-Passos et al 2001), may also involve hypoactivity of the modulatory 5HT mechanism. Depressed 5HT transmission would be due to deactivation of viscerosensory signals that convey information about deficits in extracellular fluid volume and/or body sodium to the midbrain raphe and LPBn via the NTS and area postrema.…”

“…Normally, rats show aversion to hypertonic saline at this concentration. However, as discussed in the Introduction, hypothyroid rats develop a sodium appetite (Fregly & Rowland, 1985;Belló & Covian, 1991;Ventura et al 2001;Badauê-Passos et al 2001).…”

“…Hypothyroid rats develop a sodium appetite that is correlated with renal sodium loss (Fregly & Rowland, 1985;Belló & Covian, 1991;Ventura et al 2001). Several studies have shown a depression in the activity of the renin-angiotensin-aldosterone system (RAAS) in this condition (Fregly & Rowland, 1985;Marchant et al 1993;Ventura et al 2001).…”

Chronic excitotoxic lesion of the dorsal raphe nucleus induces sodium appetite

“…Low-dose captopril treatment resulted in a higher saline intake by ibotenic DRNlesioned rats, suggesting that there is either an enhanced capacity of ANG I conversion to ANG II in forebrain structures, or an increased sensitivity to ANG II-evoked sodium appetite (24,25,(27)(28)(29). On this basis and regarding reciprocal relationships between SFO and DRN, we postulated that the presumptive angiotensinergic sensitivity of the SFO is enhanced following the failure of inhibitory signals arising from the midbrain (7,10,28).…”

“…A low dose (1 mg/g of chow) of dietary captopril (Bristol-Myers Squibb, São Paulo, SP, Brazil) was added every day to the chow from the 6th to the 11th days after surgery (PB-DRN, N = 11 and IBO-DRN, N = 10). This model promotes a systemic rise in plasma ANG I levels, which results in an elevated ANG II synthesis in circumventricular forebrain structures underlying the subsequent natriorexigenic response (24)(25)(26)(27)(28)(29). The consumption of 0.3 M NaCl and water was determined before (3-day pretreatment period), during (captopril treatment) and after treatment (9-day recovery period).…”