Cardiovascular responses evoked by activation or blockade of GABA(A) receptors in the hypothalamic PVN are attenuated in transgenic rats with low brain angiotensinogen

• Published in: Brain research Vol. 1448; pp. 101 - 110
• Main Authors: Gomes da Silva, Ana Quênia, Xavier, Carlos Henrique, Campagnole-Santos, Maria Jose, Caligiorne, Sordaini M, Baltatu, Ovidiu C, Bader, Michael, Santos, Robson Augusto S, Fontes, Marco Antônio P
• Format: Journal Article
• Language: English
• Published: Netherlands 11.04.2012
• Subjects: Angiotensinogen - deficiency; Animals; Antihypertensive Agents - pharmacology; Blood Pressure - drug effects; Brain Chemistry - drug effects; Brain Chemistry - genetics; GABA Agonists - pharmacology; GABA Antagonists - pharmacology; Gene Expression - drug effects; Heart Rate - drug effects; Hemodynamics - drug effects; Hemodynamics - physiology; Hexamethonium Compounds - pharmacology; Kidney - innervation; Kidney - physiology; Paraventricular Hypothalamic Nucleus - drug effects; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Rats, Transgenic; Receptors, GABA-A - physiology; Sympathetic Nervous System - physiology; Transgenes - genetics
• ISSN: 1872-6240
• DOI: 10.1016/j.brainres.2012.02.021

Previous evidence indicates that a balance between inhibitory gabaergic and excitatory angiotensinergic factors in the PVN is important for cardiovascular control. We investigated the cardiovascular response evoked from activation or blockade of GABA(A) receptors in the paraventricular nucleus (PVN), in transgenic rats with low brain angiotensinogen [TGR(ASrAOGEN)]. Brain Ang II and Ang-(1-7) levels were also determined. In functional experiments, TGR(ASrAOGEN) and Sprague-Dawley rats (SD, control) were anesthetized with urethane and blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded. Brain Ang II and Ang-(1-7) levels were largely reduced in TGR(ASrAOGEN) compared with SD rats. Inhibition of PVN neurons with the GABA(A) agonist, muscimol (1 nmol/100 nL), resulted in an attenuated fall in all cardiovascular variables in TGR(ASrAOGEN) compared with SD rats. This difference was particularly pronounced in HR (TGR Mus -23±6 bpm vs. -77±9 bpm SD Mus; P<0.05) and RSNA (TGR -3±10% vs.-29±8% SD; P<0.05). Furthermore, the sympathetic response evoked by blockade of GABA(A) receptors in the PVN of TGR(ASrAOGEN) was also largely suppressed. The present data indicate that the sympathetic outflow mediated by PVN neurons under basal conditions is suppressed in TGR(ASrAOGEN) rats corroborating the functional significance of brain angiotensin production in the central regulation of sympathetic output to the cardiovascular system.