Research reportNatriorexigenic effect of baclofen is reduced by AT1 receptor blockade in the lateral parabrachial nucleus

GABAA and GABAB 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 (AT1 angiotensin receptor antagonist) into the LPBN on 0.3 M 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 0.3 M 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 0.3 M 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 0.3 M 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 AT1 receptors in the LPBN, which drives rats to ingest large amounts of water and hypertonic NaCl independent if rats are fluid depleted or normohydrated.

► Activation of GABAB receptors into the LPBN increased hypertonic NaCl and water intake in fluid replete rats or FURO + CAP-treated rats. ► AT1 angiotensin receptor antagonist in the LPBN reduces sodium and water intake induced by baclofen. ► Deactivation of LPBN inhibitory mechanisms produced by baclofen in the LPBN is facilitated by ANG II acting on AT1 receptors.