Hypertension and sympathetic nervous system overactivity rely on the vascular tone of pial vessels of the rostral ventrolateral medulla in spontaneously hypertensive rats

Autor(es)

Malheiros-Lima, Milene R. ^[1] ; Antunes, Vagner R. ^[1] ; Takakura, Ana C. ^[2] ; Moreira, Thiago S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Experimental Physiology; v. 105, n. 1, p. 65-74, JAN 2020.
• Citações Web of Science: 0

Resumo

New Findings What is the central question of this study?Is purinergic signalling in the pial vessels involved in the control of vascular tone in the ventral surface of the brainstem, affecting high blood pressure and sympathetic overactivity in spontaneously hypertensive rats? What is the main finding and its importance?The regulation of vascular tone in the ventral surface of the brainstem is tailored to support neuronal functions, arterial pressure and sympathetic activity. This adds one more piece in the complex puzzle to understand the central mechanisms underlying the genesis of hypertension. Evidence suggests the rostral ventrolateral medulla (RVLM) region is chronically hypoperfused and hypoxic in spontaneously hypertensive rats (SHR), which can facilitate ATP release throughout the brainstem. Thus, we hypothesized that purinergic signalling plays a key role in the increased vascular tone in the RVLM region, which in turn could be responsible for the high sympathetic tone and blood pressure in the SHR. The application of an antagonist of P2 receptors, pyridoxalphosphate-6-azophenyl-2 `,4 `-disulfonic acid (10 mu m), or of P2Y1a receptors, MRS2179 (100 mu m), on the surface of RVLM pial vessels of SHR produced an increase in the diameter of blood vessels (PPADS: 31 +/- 1.4 mu m or MRS2179: 32 +/- 0.78 mu m vs. saline: 27 +/- 1.2 mu m), an effect not observed in normotensive Wistar rats. In addition, the antagonism of P2 receptors was able to evoke a significant decrease in the arterial pressure, heart rate and splanchnic nerve activity in SHR, but not in Wistar rats. Our data show that SHR have higher vascular tone of pial vessels in the RVLM region when compared to the normotensive Wistar rats, a mechanism that relies on purinergic signalling through P2 receptors, suggesting a possible association with higher activity of sympathoexcitatory neurones, and sustained increases in blood pressure. (AU)

• Processo FAPESP: 15/23376-1 - Núcleo retrotrapezóide, quimiossensibilidade central e automaticidade respiratória
• Beneficiário: Thiago dos Santos Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/23281-3 - Regiões encefálicas responsáveis pela neuroplasticidade observada na resposta respiratória induzida por hipercapnia em modelo animal de Doença de Parkinson
• Beneficiário: Ana Carolina Takakura Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/21991-3 - Hipertensão secundária à alta ingestão de sal: estudo da sinalização purinérgica em células neuronais do hipotálamo e sua influência na atividade do sistema nervoso autônomo e pressão arterial
• Beneficiário: Vagner Roberto Antunes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/22069-0 - Melhora nos mecanismos de regulação do fluxo sanguíneo encefálico em animais espontaneamente hipertensos: participação do exercício físico
• Beneficiário: Thiago dos Santos Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/08696-5 - Sinalização purinérgica na região do Núcleo Retrotrapezóide: contribuição para o controle respiratório no modelo de epilepsia do lobo temporal
• Beneficiário: Milene Rodrigues Malheiros Lima
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado