Increase of renal sympathetic nerve activity by metoprolol or propranolol in conscious spontaneously hypertensive rats

Majcherczyk, S; Mikulski, Andrzej; Sjölander, May; Thorén, Peter

doi:10.1111/j.1476-5381.1987.tb11267.x

Cited by 6 publications

(2 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[4][5][6][7][8][9] Of note, although they are generally characterized as inhibitors of the sympathetic nervous system, β-blockers do not reduce renal sympathetic nerve traffic. 10…”

Section: Potential Actions Of Sglt2 Inhibitors As Nephrocentric Neuro...mentioning

confidence: 99%

Critical Reanalysis of the Mechanisms Underlying the Cardiorenal Benefits of SGLT2 Inhibitors and Reaffirmation of the Nutrient Deprivation Signaling/Autophagy Hypothesis

2022

View full text Add to dashboard Cite

SGLT2 (sodium-glucose cotransporter 2) inhibitors produce a distinctive pattern of benefits on the evolution and progression of cardiomyopathy and nephropathy, which is characterized by a reduction in oxidative and endoplasmic reticulum stress, restoration of mitochondrial health and enhanced mitochondrial biogenesis, a decrease in proinflammatory and profibrotic pathways, and preservation of cellular and organ integrity and viability. A substantial body of evidence indicates that this characteristic pattern of responses can be explained by the action of SGLT2 inhibitors to promote cellular housekeeping by enhancing autophagic flux, an effect that may be related to the action of these drugs to produce simultaneous upregulation of nutrient deprivation signaling and downregulation of nutrient surplus signaling, as manifested by an increase in the expression and activity of AMPK (adenosine monophosphate–activated protein kinase), SIRT1 (sirtuin 1), SIRT3 (sirtuin 3), SIRT6 (sirtuin 6), and PGC1-α (peroxisome proliferator–activated receptor γ coactivator 1-α) and decreased activation of mTOR (mammalian target of rapamycin). The distinctive pattern of cardioprotective and renoprotective effects of SGLT2 inhibitors is abolished by specific inhibition or knockdown of autophagy, AMPK, and sirtuins. In the clinical setting, the pattern of differentially increased proteins identified in proteomics analyses of blood collected in randomized trials is consistent with these findings. Clinical studies have also shown that SGLT2 inhibitors promote gluconeogenesis, ketogenesis, and erythrocytosis and reduce uricemia, the hallmarks of nutrient deprivation signaling and the principal statistical mediators of the ability of SGLT2 inhibitors to reduce the risk of heart failure and serious renal events. The action of SGLT2 inhibitors to augment autophagic flux is seen in isolated cells and tissues that do not express SGLT2 and are not exposed to changes in environmental glucose or ketones and may be related to an ability of these drugs to bind directly to sirtuins or mTOR. Changes in renal or cardiovascular physiology or metabolism cannot explain the benefits of SGLT2 inhibitors either experimentally or clinically. The direct molecular effects of SGLT2 inhibitors in isolated cells are consistent with the concept that SGLT2 acts as a nutrient surplus sensor, and thus, its inhibition causes enhanced nutrient deprivation signaling and its attendant cytoprotective effects, which can be abolished by specific inhibition or knockdown of AMPK, sirtuins, and autophagic flux.

show abstract

“…[4][5][6][7][8][9] Of note, although they are generally characterized as inhibitors of the sympathetic nervous system, β-blockers do not reduce renal sympathetic nerve traffic. 10…”

Section: Potential Actions Of Sglt2 Inhibitors As Nephrocentric Neuro...mentioning

confidence: 99%

Critical Reanalysis of the Mechanisms Underlying the Cardiorenal Benefits of SGLT2 Inhibitors and Reaffirmation of the Nutrient Deprivation Signaling/Autophagy Hypothesis

2022

View full text Add to dashboard Cite

show abstract

“…21 In this study, SHR was treated with metoprolol for 4 weeks. 21 In this study, SHR was treated with metoprolol for 4 weeks.…”

Section: Introductionmentioning

confidence: 99%

Metoprolol Restores Expression and Vasodilatation Function of AT2R in Spontaneously Hypertensive Rats

Huang

et al. 2014

Journal of Cardiovascular Pharmacology

View full text Add to dashboard Cite

Angiotensin II type 2 receptor (AT2R) is thought as an important regulatory target during antihypertensive treatment but its role in vasomotor regulation remains controversial. The interactional relationship between the sympathetic nervous systems and the renin-angiotensin-aldosterone system (RAS) has been revealed but poorly investigated. This work was designed to explore the effect of metoprolol (MET) treatment on the RAS, especially the expression and vasomotor function of AT2R, in spontaneously hypertensive rats (SHR). The results showed that upregulated renin activity and Ang II concentration of plasma in SHR were inhibited by MET treatment. In isolated superior mesenteric arteries from both Wistar-Kyoto rats and SHR, Ang II perfusion induced vasodilatation after AT1R inhibition by telmisartan, although the vasodilatation was harmed in SHR. Furthermore, AT2R inhibitor PD123319 arrested the vasodilatation induced by Ang II. SHR received MET exerted improved vasodilatation mediated by AT2R (47.29% ± 5.16% vs. 24.99% ± 4.93% for MET and SHR, respectively; P < 0.05). Western blot analysis showed that MET restored expression of AT2R in SHR, which may contribute to MET's antihypertensive effect. These results suggested an impact of β-adrenergic blocker on RAS and supported an important role of AT2R in antihypertensive treatment.

show abstract

β-Blockers

Conway¹,

Bilski²

1990

Pharmacology of Antihypertensive Therapeutics

View full text Add to dashboard Cite

Increase of renal sympathetic nerve activity by metoprolol or propranolol in conscious spontaneously hypertensive rats

Cited by 6 publications

References 9 publications

Critical Reanalysis of the Mechanisms Underlying the Cardiorenal Benefits of SGLT2 Inhibitors and Reaffirmation of the Nutrient Deprivation Signaling/Autophagy Hypothesis

Critical Reanalysis of the Mechanisms Underlying the Cardiorenal Benefits of SGLT2 Inhibitors and Reaffirmation of the Nutrient Deprivation Signaling/Autophagy Hypothesis

Metoprolol Restores Expression and Vasodilatation Function of AT2R in Spontaneously Hypertensive Rats

β-Blockers

Contact Info

Product

Resources

About