Renal sympathetic activation triggered by the rostral ventrolateral medulla is dependent of spinal cord AT1 receptors in Goldblatt hypertensive rats

Milanez, Maycon I.O.; Nishi, Érika E.; Mendes, Rodrigo; Rocha, Antônio A. de A.; Bergamaschi, Cássia Toledo; Campos, Rui

doi:10.1016/j.peptides.2021.170660

Cited by 3 publications

(3 citation statements)

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“…shown that these changes depend on the activation of Angiotensin II type 1 (AT1) receptors in the spinal cord (Milanez et al, 2021(Milanez et al, , 2020a(Milanez et al, , 2018. In the present work, we take advantage of this approach in a Goldblatt two-kidney, one-clip (2K1C) rat hypertension model to advance the understanding of how the PVN controls sympathetic vasomotor activity in normal and hypertensive rats addressing the territorially differential changes in the frequency parameters of the basal and bursting activities of the renal (rSNA) and splanchnic (sSNA) sympathetic nerves in hypertensive and normal rats during disinhibition of PVN by local microinjection of bicuculline.…”

Section: Introductionmentioning

confidence: 99%

“…The desinhibition of the PVN through local microinjection of the γ-aminobutyric acid (GABA)-ergic antagonist bicuculline triggers both a robust pressor response and changes in the sympathetic vasomotor activity pattern to the renal, splanchnic and lumbar territories, generating low-frequency bursts unsynchronized to the cardiac cycle (Kenney et al, 2001). It has been shown that these changes depend on the activation of Angiotensin II type 1 (AT1) receptors in the spinal cord (Milanez et al, 2021, 2020a, 2018). In the present work, we take advantage of this approach in a Goldblatt two-kidney, one-clip (2K1C) rat hypertension model to advance the understanding of how the PVN controls sympathetic vasomotor activity in normal and hypertensive rats addressing the territorially differential changes in the frequency parameters of the basal and bursting activities of the renal (rSNA) and splanchnic (sSNA) sympathetic nerves in hypertensive and normal rats during disinhibition of PVN by local microinjection of bicuculline.…”

Section: Introductionmentioning

confidence: 99%

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Frequency-coded patterns of sympathetic vasomotor activity are differentially evoked by the paraventricular nucleus of the hypothalamus in the Goldblatt hypertension model

Faber

Oliver

Simoes

et al. 2023

Preprint

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The activation of specific brain areas involved in regulating the vasomotor sympathetic activity can lead to distinct effects in the postganglionic nerves in both physiological and pathological conditions, suggesting that the sympathetic vasomotor activity is differentially coded depending on the nerve outflow and the target organs. Previous studies investigating such patterns have mostly focused on the global energy of the signal. However, recent evidence has suggested that relevant information is coded in the power distribution along the frequency range. Disturbing the sympathoexcitatory vasomotor tone in the paraventricular nucleus of the hypothalamus (PVN) allows to investigate the sympathetic nerve activity in overloaded conditions in both hypertensive and control animals. By disinhibiting the PVN through the microinjection of bicuculline, an antagonist of γ-aminobutyric acid type A (GABAa) receptors, in the Goldblatt (2K1C) rat model of hypertension we addressed the territorially differential changes in the frequency parameters of the renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively). We also tested the effect of the systemic administration of losartan, an antagonist of the angiotensin II type 1 receptors (AT1), in the attenuation of the increased rSNA and sSNA in 2K1C rats, once these changes are reported to be dependent on the AT1 activation in the Goldblatt model. Our results revealed that each nerve activity presents its own electrophysiological pattern of frequency-coded rhythm in each group, in basal condition and after bicuculline microinjection, but with no significant differences regarding total power comparison among groups. Additionally, the 2K1C animals treated with losartan showed no decrease in the hypertensive response triggered by the GABAa antagonism when compared to the non-treated 2K1C group. However, their spectral patterns of sympathetic nerve activity were different from the other two groups, suggesting that the systemic blockade of AT1 receptors does not totally recover the basal levels of neither the autonomic symptoms nor the electrophysiological patterns in the Goldblatt model, but act on their spectral frequency distribution. These results suggest that the differential responses evoked by the PVN were preferentially coded in frequency of vasomotor sympathetic responses, indicating that the PVN distinctly modulated each rhythmic activity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Frequency-coded patterns of sympathetic vasomotor activity are differentially evoked by the paraventricular nucleus of the hypothalamus in the Goldblatt hypertension model

Faber

Oliver

Simoes

et al. 2023

Preprint

Self Cite

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“…On the other hand, local GABAergic agonism significantly reduces rSNA (Zhang and Patel, 1998). The changes triggered by bicuculline are, in part, dependent on the activation of Angiotensin II type 1 (AT1) receptors (Milanez et al, 2018(Milanez et al, , 2020a(Milanez et al, , 2021, as the microinjection of the AT1 receptor antagonist losartan into the PVN has been reported to blunt the sympathoexcitation evoked by local GABAergic antagonism (Chen and Toney, 2003). GABAergic neurons are, thus, crucial for the PVN cardiovascular function through peripheral sympathetic discharges.…”

Section: Introductionmentioning

confidence: 99%

Frequency-coded patterns of sympathetic vasomotor activity are differentially evoked by the paraventricular nucleus of the hypothalamus in the Goldblatt hypertension model

Faber,

Milanez,

Simões

et al. 2023

Front. Cell. Neurosci.

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IntroductionThe paraventricular nucleus of the hypothalamus (PVN) contains premotor neurons involved in the control of sympathetic vasomotor activity. It is known that the stimulation of specific areas of the PVN can lead to distinct response patterns at different target territories. The underlying mechanisms, however, are still unclear. Recent evidence from sympathetic nerve recording suggests that relevant information is coded in the power distribution of the signal along the frequency range. In the present study, we addressed the hypothesis that the PVN is capable of organizing specific spectral patterns of sympathetic vasomotor activation to distinct territories in both normal and hypertensive animals.MethodsTo test it, we investigated the territorially differential changes in the frequency parameters of the renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively), before and after disinhibition of the PVN by bicuculline microinjection. Subjects were control and Goldblatt rats, a sympathetic overactivity-characterized model of neurogenic hypertension (2K1C). Additionally, considering the importance of angiotensin II type 1 receptors (AT1) in the sympathetic responses triggered by bicuculline in the PVN, we also investigated the impact of angiotensin AT1 receptors blockade in the spectral features of the rSNA and sSNA activity.ResultsThe results revealed that each nerve activity (renal and splanchnic) presents its own electrophysiological pattern of frequency-coded rhythm in each group (control, 2K1C, and 2K1C treated with AT1 antagonist losartan) in basal condition and after bicuculline microinjection, but with no significant differences regarding total power comparison among groups. Additionally, the losartan 2K1C treated group showed no decrease in the hypertensive response triggered by bicuculline when compared to the non-treated 2K1C group. However, their spectral patterns of sympathetic nerve activity were different from the other two groups (control and 2K1C), suggesting that the blockade of AT1 receptors does not totally recover the basal levels of neither the autonomic responses nor the electrophysiological patterns in Goldblatt rats, but act on their spectral frequency distribution.DiscussionThe results suggest that the differential responses evoked by the PVN were preferentially coded in frequency, but not in the global power of the vasomotor sympathetic responses, indicating that the PVN is able to independently control the frequency and the power of sympathetic discharges to different territories.

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Regulation of sympathetic nerve activity by the central angiotensin system in heart failure

Shanks

Ramchandra

2023

Angiotensin

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Renal sympathetic activation triggered by the rostral ventrolateral medulla is dependent of spinal cord AT1 receptors in Goldblatt hypertensive rats

Cited by 3 publications

References 41 publications

Frequency-coded patterns of sympathetic vasomotor activity are differentially evoked by the paraventricular nucleus of the hypothalamus in the Goldblatt hypertension model

Frequency-coded patterns of sympathetic vasomotor activity are differentially evoked by the paraventricular nucleus of the hypothalamus in the Goldblatt hypertension model

Frequency-coded patterns of sympathetic vasomotor activity are differentially evoked by the paraventricular nucleus of the hypothalamus in the Goldblatt hypertension model

Regulation of sympathetic nerve activity by the central angiotensin system in heart failure

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