Key result
Angiotensin II drives superoxide-dependent RVLM BDNF upregulation to protect against oxidative stress and pressor response.
Why the study?
Oxidative stress in the rostral ventrolateral medulla contributes to neurogenic hypertension, and the role of brain-derived neurotrophic factor in this process is unclear.
Does Angiotensin II-induced BDNF upregulation in the RVLM protect against oxidative stress and long-term pressor response in Wistar-Kyoto rats?
Does Angiotensin II-induced BDNF upregulation in the RVLM protect against oxidative stress and long-term pressor response in Wistar-Kyoto rats?
Angiotensin II upregulates BDNF in the RVLM, which acts as a negative-feedback mechanism to protect against oxidative stress and neurogenic hypertension.
BDNF/TrkB signaling may limit Ang II-driven oxidative stress in RVLM; leaves open its therapeutic relevance in human neurogenic hypertension.
RATIONALE: Oxidative stress in rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons for the maintenance of neurogenic vasomotor tone are located, contributes to neural mechanisms of hypertension. Emerging evidence suggests that brain-derived neurotrophic factor (BDNF) manifests "nontrophic" actions. OBJECTIVE: We assessed the hypothesis that BDNF plays an active role in oxidative stress-associated neurogenic hypertension by maintaining superoxide anion (O⁻(.)₂) homeostasis in RVLM. METHODS AND RESULTS: In Wistar-Kyoto rats, microinjection of angiotensin II (Ang II) bilaterally into RVLM upregulated BDNF mRNA and protein and induced cAMP response element binding protein (CREB) phosphorylation. The Ang II-induced BDNF upregulation in RVLM was attenuated by coadministration of the NADPH oxidase inhibitor apocynin; the superoxide dismutase mimetic tempol; or an antisense oligonucleotide against CREB. Intracisternal infusion of Ang II elicited phosphorylation of p47(phox) subunit of NADPH oxidase, suppression of mitochondrial electron coupling capacity, and augmentation in mitochondrial uncoupling protein (UCP)2 expression in RVLM. The former 2 cellular events were enhanced, whereas UCP2 upregulation was attenuated by gene knockdown of BDNF or depletion of tropomyosin receptor kinase (Trk)B ligands with recombinant human TrkB-Fc fusion protein. The same treatments also significantly potentiated both Ang II-induced (O⁻(.)₂) production in RVLM and chronic pressor response. CONCLUSIONS: Ang II induces (O⁻(.)₂) -dependent upregulation of BDNF in RVLM via phosphorylation of CREB. The Ang II-activated BDNF/TrkB signaling, in turn, exerts negative-feedback regulation on tissue (O⁻(.)₂) level in RVLM through inhibition of p47(phox) phosphorylation, preservation of mitochondrial electron transport capacity, and upregulation of mitochondrial UCP2, resulting in protection against Ang II-induced oxidative stress and long-term pressor response.
No takes yet. Share an insight, caveat, or question.
Chan et al. (2010) studied Hypertension. Angiotensin II microinjection was evaluated on BDNF mRNA and protein upregulation, CREB phosphorylation, and superoxide anion production. Angiotensin II induces superoxide-dependent upregulation of BDNF in the RVLM, which exerts negative-feedback regulation to protect against oxidative stress and long-term pressor response.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: