skip to main content
Idioma:

Thoracic TRPV1 Receptor Spinal Afferent Ablation Prevents the Development and Progression of Hypertension in SHR but Not in Ang II‐infused Rats

Shanks, Julia A. ; Morais, Sharon Del Bem Velloso ; Wang, Hanjun ; Zucker, Irving H.

The FASEB journal, 2018-04, Vol.32 (S1), p.885.4-885.4 [Periódico revisado por pares]

The Federation of American Societies for Experimental Biology

Texto completo disponível

Citações Citado por
  • Título:
    Thoracic TRPV1 Receptor Spinal Afferent Ablation Prevents the Development and Progression of Hypertension in SHR but Not in Ang II‐infused Rats
  • Autor: Shanks, Julia A. ; Morais, Sharon Del Bem Velloso ; Wang, Hanjun ; Zucker, Irving H.
  • É parte de: The FASEB journal, 2018-04, Vol.32 (S1), p.885.4-885.4
  • Descrição: Sympatho‐excitation is well described in the pathogenesis of hypertension in both clinical and animal models. Increased sympathetic drive to the heart and alerted cardiac spinal afferent signaling have previously been implicated in contributing to the development and progression of hypertension via the cardiac sympathetic afferent reflex (CSAR). However, the role cardiac spinal afferents play in modulating this response is unknown. To address this, we utilized two rat models of hypertension that have previously been described to have a neurogenic component to their phenotype, the spontaneously hypertension rat (SHR) and angiotensin II (Ang II; 240 ng/kg/min) infusion model. To selectively and chronically ablate the CSAR, the afferent specific neurotoxin, a potent TRPV1 receptor agonist, Resiniferatoxin (RTX) was given epidurally at the level of the T1–T4 dorsal root ganglia (DRG; 6 μg/ml, 10 μl/per ganglion). Blood pressure (BP) was monitored using radiotelemetry in the conscious state before and for 1–2 months post RTX. Echocardiograms were performed on all animals, under 2% isoflurane anesthesia, pre‐treatment and at the end of the study to monitor any changes spinal nerve ablation had on cardiac function. Selective ablation of TRPV1 expressing neurons in the DRG was confirmed by immunohistochemistry. In young (8 week) SHR, T1–T4 RTX abolished the increase in blood pressure (BP) observed in vehicle control animals (n = 6, both groups). Thoracic TRPV1 ablation with RTX in older (16 week) SHR with established hypertension significantly reduced BP compared to control (n = 7, both groups). No change in BP to thoracic RTX was observed in Wistar Kyoto rats (n = 5, RTX and control), RTX had no effect on heart rate in any group. To confirm the BP lowering action of RTX in the SHR was site specific to the T1–T4 thoracic (cardiac) DRG, RTX was administered into the lumbar region of the spinal cord (L2–L5) in 16‐week‐old SHR; no change in BP was observed (n = 5, RTX and control). Epicardial application of RTX in 16 week‐old SHR also failed to significantly reduce BP compared to control (n = 6, both groups). RTX treatment 1 week before (n = 3) or 1 week after (n = 5) Ang II infusion did not alter Ang II‐induced hypertension compared to controls (n=3; n=8, respectively). These data suggest that thoracic spinal afferents contribute to the hypertensive process in SHR. We speculate that the SHR exhibit higher levels of sympatho‐excitation compared to Ang II‐hypertension, thereby responding more effectively to elimination of a sympatho‐excitatory input. From these data, the origin of the afferents is inconclusive. Support or Funding Information Supported by NIH grant HL 126796 and Sorrento Therapeutics, Inc. This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal.
  • Editor: The Federation of American Societies for Experimental Biology
  • Idioma: Inglês
Voltar para lista de resultados

  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

Buscando em bases de dados remotas. Favor aguardar.