Natriorexigenic effect of baclofen is reduced by AT1 receptor blockade in the lateral parabrachial nucleus.

GABA(A) and GABA(B) receptors activation with agonists muscimol and baclofen, respectively in the lateral parabrachial nucleus (LPBN), induces water and hypertonic NaCl intake in rats. The purpose of this study was to examine the effects of previous injections of losartan (AT(1) angiotensin receptor antagonist) into the LPBN on 0.3M NaCl and water intake induced by baclofen injected bilaterally in the same area in fluid replete rats and in rats treated with the diuretic furosemide combined with a low dose of the angiotensin-converting enzyme inhibitor captopril injected subcutaneously. Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used. Bilateral injections of baclofen (0.5 nmol/0.2 µl, n=6) into the LPBN in fluid replete rats induced 0.3M NaCl intake (22.4 ± 6.5 vs. saline: 0.1 ± 0.1 ml/210 min) and water intake (14.2 ± 4.0 vs. saline: 0.6 ± 0.6 ml/210 min) and pre-treatment of the LPBN with losartan (50 µg/0.2 µl) reduced 0.3M NaCl intake (7.4 ± 7.0 ml/210 min) and water intake (2.8 ± 2.4 ml/210 min) induced by baclofen. In rats treated with furosemide+captopril, pre-treatment with losartan into the LPBN attenuated the increase in 0.3M NaCl intake (13.3 ± 3.2 vs. saline+baclofen: 24.3 ± 3.9 ml/180 min) and water intake (4.8 ± 2.1 vs. saline+baclofen: 19.5 ± 6.6 ml/180 min) produced by baclofen. We conclude that baclofen may produce a non-specific blockade of the inhibitory mechanisms of LPBN (deactivation of LPBN inhibitory mechanisms) and this blockade is facilitated by angiotensin II acting on AT(1) receptors in the LPBN, which drives rats to ingest large amounts of water and hypertonic NaCl independent if rats are fluid depleted or normohydrated.

Sodium intake by hyperosmotic rats treated with a GABA(A) receptor agonist into the lateral parabrachial nucleus.

Inhibitory mechanisms in the lateral parabrachial nucleus (LPBN) and central GABAergic mechanisms are involved in the regulation of water and NaCl intake. Besides increasing fluid depletion-induced sodium intake, the activation of GABA(A) receptors with muscimol into the LPBN also induces ingestion of 0.3 M NaCl in normonatremic, euhydrated rats. It has been suggested that inhibitory mechanisms activated by osmotic signals are blocked by GABA(A) receptor activation in the LPBN, thereby increasing hypertonic NaCl intake. Therefore, in the present study we investigated the effects of muscimol injected into the LPBN on water and 0.3 M NaCl intake in hyperosmotic cell-dehydrated rats (rats treated with an intragastric load of 2 M NaCl). Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used. In euhydrated rats, muscimol (0.5 nmol/0.2 microl), bilaterally injected into the LPBN, induced ingestion of 0.3 M NaCl (24.6+/-7.9 vs. vehicle: 0.5+/-0.3 ml/180 min) and water (6.3+/-2.1 vs. vehicle: 0.5+/-0.3 ml/180 min). One hour after intragastric 2 M NaCl load (2 ml), bilateral injections of muscimol into the LPBN also induced 0.3 M NaCl intake (22.1+/-5.2 vs. vehicle: 0.9+/-0.8 ml/210 min) and water intake (16.5+/-3.6 vs. vehicle: 7.8+/-1.8 ml/210 min). The GABA(A) antagonist bicuculline (0.4 nmol/0.2 microl) into the LPBN reduced the effect of muscimol on 0.3 M NaCl intake (7.1+/-2.1 ml/210 min). Therefore, the activation of GABA(A) receptors in the LPBN induces ingestion of 0.3 M NaCl by hyperosmotic cell-dehydrated rats, suggesting that plasma levels of renin or osmolarity do not affect sodium intake after the blockade of LPBN inhibitory mechanisms with muscimol.