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

Silva, Ana Quenia Gomes da; Xavier, Carlos Henrique; Campagnole‐Santos, Maria José; Caligiorne, Sordaini Maria; Baltatu, Ovidiu Constantin; Bäder, Michael; Santos, Robson Augusto Souza; Fontes, Marco Antônio Peliky

doi:10.1016/j.brainres.2012.02.021

Cited by 34 publications

(20 citation statements)

References 39 publications

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“…Thus, we used hexamethonium-induced reduction in RSNA as a marker of the sympathetic excitation based on the previous report. 17 The hexamethonium-induced reductions in RSNA and mean arterial blood pressure in CKD rats (at 0 and 2 weeks) were significantly increased, compared with those seen in sham rats. We demonstrated that the renal venous norepinephrine concentration correlated significantly with renal injury in our previous study.…”

Section: Discussionmentioning

confidence: 85%

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Involvement of Renal Sympathetic Nerve Overactivation in the Progression of Chronic Kidney Disease in Rats

Kobuchi

Tanaka

Funai

et al. 2014

Journal of Cardiovascular Pharmacology

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Time-dependent changes in the renal sympathetic nerve activity (RSNA) in the progression of chronic kidney disease (CKD) have not been investigated, despite the fact that renal sympathetic nervous system is augmented in the condition of CKD. In the present study, we examined time-dependent changes in RSNA and renal venous norepinephrine concentrations for 12 weeks using 5 of 6 nephrectomized CKD rats. Both RSNA and norepinephrine concentrations were increased during the early phase in the progression of CKD. Urinary protein excretion and systolic blood pressure (SBP) were gradually increased during 12 weeks after 5 of 6 nephrectomy. Treatment with γ-aminobutyric acid or the combination of prazosin and propranolol in the early phase (0-4 weeks) after 5 of 6 nephrectomy significantly attenuated the increases in urinary protein excretion and SBP in 5 of 6 nephrectomized rats. On the other hand, the same treatment in the late phase (8-12 weeks) after 5 of 6 nephrectomy failed to suppress the proteinuria and increase in SBP. Treatment with hydralazine at hypotensive dose for 12 weeks also failed to affect the proteinuria in 5 of 6 nephrectomized CKD rats. In conclusion, the augmentation of renal sympathetic nervous system in early phase after 5 of 6 nephrectomy is closely related to the development of partial ablation-induced CKD in rats.

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Section: Discussionmentioning

confidence: 85%

“…In the present study, we used hexamethoniuminduced reduction in RSNA as a marker of sympathetic outflow based on the previous report. 17 The rats were killed by an overdose of potassium chloride at the end of each experiment to determine the background noise in the dead rats.…”

Section: Renal Nerve Recordingmentioning

confidence: 99%

Involvement of Renal Sympathetic Nerve Overactivation in the Progression of Chronic Kidney Disease in Rats

Kobuchi

Tanaka

Funai

et al. 2014

Journal of Cardiovascular Pharmacology

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“…13 Deletion of AGT specifically in the brain of mice and rats decreases BP and SNA. 20–23 Thus, without a control mechanism, the generation of extracellular ANG may directly activate AT 1 receptors in this region of the brain leading to increased sympathetic outflow. 24 Consequently, expression of renin-b might provide a counter regulatory control mechanism preventing widespread conversion of extracellular AGT to ANG peptides.…”

Section: Discussionmentioning

confidence: 99%

Selective Deletion of the Brain-Specific Isoform of Renin Causes Neurogenic Hypertension

et al. 2016

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The renin-angiotensin system (RAS) in the brain is a critical determinant of blood pressure but the mechanisms regulating RAS activity in the brain remain unclear. Expression of brain renin (renin-b) occurs from an alternative promoter-first exon. The predicted translation product is a non-secreted enzymatically active renin whose function is unknown. We generated a unique mouse model by selectively ablating the brain-specific isoform of renin (renin-b) while preserving expression and function of the classical isoform expressed in the kidney (renin-a). Preservation of renal renin was confirmed by measurements of renin gene expression and immunohistochemistry. Surprisingly, renin-b-deficient mice exhibited hypertension, increased sympathetic nerve activity to the kidney and heart, and impaired baroreflex sensitivity. Whereas these mice displayed decreased circulating RAS activity, there was a paradoxical increase in brain RAS activity. Physiologically, renin-b-deficient mice exhibited an exaggerated depressor response to intracerebroventricular administration of losartan, captopril or aliskiren. At the molecular level, renin-b-deficient mice exhibited increased expression of AT1 receptor in the paraventricular nucleus, which correlated with an increased renal sympathetic nerve response to leptin which was dependent upon AT1 receptor activity. Interestingly, despite an ablation of renin-b expression, expression of renin-a was significantly increased in rostral ventral lateral medulla. These data support a new paradigm for the genetic control of RAS activity in the brain by a coordinated regulation of the renin isoforms, with expression of renin-b tonically inhibiting expression of renin-a under baseline conditions. Impairment of this control mechanism causes neurogenic hypertension.

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“…These seemingly inconsistent results can be attributed to the fine-tuning role of AngII on behavioural responses, which may induce opposite effects depending on the concentration, brain region and experimental setting [49][50][51]. On the other hand, these two transgenic lineages showed lower levels of Ang-(1-7) in different areas of the brain [52,53], suggesting that lower Ang-(1-7) or a misbalance between the two peptides in particular regions may account for the behavioural impairment described in these transgenic lines. Future studies will be necessary to identify the role of each angiotensin peptide in specific brain regions related to psychiatric disorders, such as anxiety and depression.…”

Section: Discussionmentioning

confidence: 99%

Anxiolytic- and antidepressant-like effects of angiotensin-(1–7) in hypertensive transgenic (mRen2)27 rats

et al. 2016

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Angiotensin-(1-7) [Ang-(1-7)], a counter-regulatory peptide of the renin-angiotensin system (RAS) exerts its effects through the G-protein-coupled receptor Mas, which is expressed in different tissues, including the brain. Ang-(1-7) has a broad range of effects beyond the well-described cardiovascular and renal actions, including the modulation of emotional and behavioural responses. In the present study we tested the hypothesis that Ang-(1-7) could attenuate the anxiety- and depression-like behaviours observed in transgenic hypertensive (mRen2)27 rats (TGRs). We also hypothesized that Ang-(1-7) could be involved in the anxiolytic-like effect induced by ACE (angiotensin-converting enzyme) treatment in these hypertensive rats. Therefore, TGRs and Sprague-Dawley rats were subjected to the Elevated Plus Maze (EPM) test, Forced Swimming Test (FST) and Novelty Suppressed Feeding (NSF). TGRs presented a decreased percentage of entries in the open arms of the EPM test, a phenotype reversed by systemic treatment with enalapril or intracerebroventricular infusion of Ang-(1-7). It is interesting that pre-treatment with A779, a selective Mas receptor antagonist, prevented the anxiolytic-like effect induced by the ACE inhibitor. In the NSF test, TGRs showed increased latency to eating, an indicative of a higher aversion in response to a new environment. These animals also showed increased immobility in the FST. Again, Ang-(1-7) reversed this phenotype. Thus, our data showed that Ang-(1-7) can modulate anxiety- and depression-like behaviours in TGRs and warrant further investigation as a new therapy for certain psychiatric disorders.

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

Cited by 34 publications

References 39 publications

Involvement of Renal Sympathetic Nerve Overactivation in the Progression of Chronic Kidney Disease in Rats

Involvement of Renal Sympathetic Nerve Overactivation in the Progression of Chronic Kidney Disease in Rats

Selective Deletion of the Brain-Specific Isoform of Renin Causes Neurogenic Hypertension

Anxiolytic- and antidepressant-like effects of angiotensin-(1–7) in hypertensive transgenic (mRen2)27 rats

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