Acute renal denervation normalizes aortic function and decreases blood pressure in spontaneously hypertensive rats

Moreira, Nathalia Juocys Dias; Santos, Fernando dos; Moreira, Edson Dias; Farah, Daniela; Souza, Leandro Franco de; Silva, Maikon Barbosa da; Moraes‐Silva, Ivana C.; Lincevicius, Gisele S.; Caldini, Élia Garcia; Irigoyen, Maria Cláudia

doi:10.1038/s41598-020-78674-8

Cited by 6 publications

(3 citation statements)

References 81 publications

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“…Selective afferent renal denervation has no effect on baseline BP in these rats, thus, renal efferents control baseline BP (Banek et al, 2016; Foss et al, 2015; Jacob et al, 2003; Osborn & Foss, 2017). However, other studies denervated the same rat strain and found no baseline BP alterations, which is compatible to findings from other rat strains and mice (Asirvatham‐Jeyaraj et al, 2016; Foss et al, 2018; Gueguen et al, 2019; Hohl et al, 2022; Moreira et al, 2020; Xiao et al, 2015). Further studies have to be performed to test if the species and/or background strain or rather technical issues like denervation efficacy are decisive.…”

Section: Discussionsupporting

confidence: 87%

Angiotensin deficient FVB/N mice are normotensive

Rodrigues

Todiraș

Qadri

et al. 2023

British J Pharmacology

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Background and Purpose All previous rodent models lacking the peptide hormone angiotensin II (Ang II) were hypotensive. A mixed background strain with global deletion of the angiotensinogen gene was backcrossed to the FVB/N background (Agt‐KO), a strain preferred for transgenic generation. Surprisingly, the resulting line turned out to be normotensive. Therefore, this study aimed to understand the unique blood pressure regulation of FVB/N mice without angiotensin peptides. Experimental Approach Acute and chronic recordings of blood pressure (BP) in freely‐moving adult mice were performed to establish baseline BP. The pressure responses to sympatholytic and sympathomimetic as well as a nitric oxide inhibitor and donor compounds were used to quantify the neurogenic tone and endothelial function. The role of the renal nerves on baseline BP maintenance was tested by renal denervation. Finally, further phenotyping was done by gene expression analysis, histology and measurement of metabolites in plasma, urine and tissues. Key Results Baseline BP in adult FVB/N Agt‐KO was unexpectedly unaltered. As compensatory mechanisms Agt‐KO presented an increased sympathetic nerve activity and reduced endothelial nitric oxide production. However, FVB/N Agt‐KO exhibited the renal morphological and physiological alterations previously found in mice lacking the production of Ang II including polyuria and hydronephrosis. The hypotensive effect of bilateral renal denervation was blunted in Agt‐KO compared to wildtype FVB/N mice. Conclusion and Implications We describe a germline Agt‐KO line that challenges all previous knowledge on BP regulation in mice with deletion of the classical RAS. This line may represent a model of drug‐resistant hypertension because it lacks hypotension.

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Section: Discussionsupporting

confidence: 87%

Angiotensin deficient FVB/N mice are normotensive

Rodrigues

Todiraș

Qadri

et al. 2023

British J Pharmacology

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“…Moreover, WKY rats had earlier reductions in cardiac function when compared with Wistar rats. Due to these factors, some authors have actually used or suggested the use of Wistar rats as a control for SHR in several conditions [ 31 , 34 , 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Hypertension on the Recovery of Renal Dysfunction following Reversal of Unilateral Ureteral Obstruction in the Rat

Hammad

Lubbad

Al‐Salam

et al. 2023

IJMS

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Both ureteral obstruction (UO) and hypertension are common conditions that affect kidney functions. Hypertension and chronic kidney disease are closely associated with an overlapping and intermingled cause-and-effect relationship. The effect of hypertension on the renal dysfunction following reversible UO has not been studied previously. To study this effect, spontaneously hypertensive (G-HT, n = 10) and normotensive Wistar (G-NT, n = 10) rats underwent 48-h reversible left unilateral UO (UUO), and the effect of UUO was studied 96 h following UUO reversal. The glomerular filtration rate, renal blood flow, and renal tubular functions such as the fractional excretion of sodium in the post-obstructed left kidney (POK) in both groups were significantly altered compared with the non-obstructed right kidney (NOK). However, the alterations in the G-HT were significantly more exaggerated when compared with the G-NT. Similar findings were observed with the histological features, gene expression of kidney injury markers, pro-inflammatory, pro-fibrotic and pro-apoptotic cytokines, and pro-collagen, as well as tissue levels of apoptotic markers. We conclude that hypertension has significantly exaggerated the alterations in renal functions and other parameters of renal injury associated with UUO.

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“…It has been reported that renal denervation does not significantly alter arterial pressure in spontaneously hypertensive rats (SHR) over a short period of 1 h, despite interfering with intrarenal function (such as increasing RBF, dynamic autoregulation of RBF, and variability of RBF). [ 74 ] Meanwhile, despite causing systemic hypotension, RSDN does not affect perfusion and renal function at various intervals (directly and after 3 months) and does not alter RBF in patients with hypertension. [ 75 ] Hence, it can be deduced that the effect of RSDN is negligible on acute or chronic renal perfusion.…”

Section: Renal Sympathetic Denervation and Renal Blood Flowmentioning

confidence: 99%

The denervation or activation of renal sympathetic nerve and renal blood flow

Nematbakhsh,

Kharazmi,

Hosseini-Dastgerdi

et al. 2023

J Res Med Sci

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The denervation or activation of the sympathetic nerve in the kidney can affect renal hemodynamics. The sympathetic nervous system regulates the physiological functions of the kidneys. Stimulation of sympathetic efferent nerves affects various parameters related to renal hemodynamics, including sodium excretion, renin secretion, and renal blood flow (RBF). Hence, renal sympathetic fibers may also play an essential role in regulating systemic vascular resistance and controlling blood pressure. In the absence of renal nerves, the hemodynamics response to stimuli is negligible or absent. The effect of renal sympathetic denervation on RBF is dependent on several factors such as interspecies differences, the basic level of nerve activity in the vessels or local density of adrenergic receptor in the vascular bed. The role of renal denervation has been investigated therapeutically in hypertension and related disorders. Hence, the dynamic impact of renal nerves on RBF enables using RBF dynamic criteria as a marker for renal denervation therapy.

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Acute renal denervation normalizes aortic function and decreases blood pressure in spontaneously hypertensive rats

Cited by 6 publications

References 81 publications

Angiotensin deficient FVB/N mice are normotensive

Angiotensin deficient FVB/N mice are normotensive

The Effect of Hypertension on the Recovery of Renal Dysfunction following Reversal of Unilateral Ureteral Obstruction in the Rat

The denervation or activation of renal sympathetic nerve and renal blood flow

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