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

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: Experimental Physiology; v. 105, n. 1, p. 65-74, JAN 2020.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 15/23376-1 - Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity
• Grantee: Thiago dos Santos Moreira
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 16/23281-3 - Encephalic regions responsible for neuroplasticity observed in respiratory response induced by hypercapnia in a modelo of Parkinson's Disease
• Grantee: Ana Carolina Thomaz Takakura
• Support type: Regular Research Grants
• FAPESP's process: 16/21991-3 - Salt-induced hypertension: role of purinergic signaling in the neuronal cells at the hypothalamus level, and its correlation with the autonomic nervous system and blood pressure control
• Grantee: Vagner Roberto Antunes
• Support type: Regular Research Grants
• FAPESP's process: 16/22069-0 - Amelioration of the brainstem vascular imbalances in an spontaneously hypertensive rats with exercise
• Grantee: Thiago dos Santos Moreira
• Support type: Regular Research Grants
• FAPESP's process: 17/08696-5 - Purinergic signalling within the Retrotrapezoid Nucleus region: role of breathing control in the temporal lobe epilepsy model
• Grantee: Milene Rodrigues Malheiros Lima
• Support type: Scholarships in Brazil - Post-Doctorate