P2Y1 Receptors Expressed by C1 Neurons Determine Peripheral Chemoreceptor Modulation of Breathing, Sympathetic Activity, and Blood Pressure

Author(s)

Wenker, Ian C. ^[1] ; Sobrinho, Cleyton R. ^[2] ; Takakura, Ana C. ^[3] ; Mulkey, Daniel K. ^[1] ; Moreira, Thiago S. ^[2]

Affiliation

^[1] Univ Connecticut, Dept Physiol & Neurobiol, Storrs, CT 06269 - USA

^[2] Univ Sao Paulo, Dept Physiol & Biophys, BR-05508000 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Dept Pharmacol, BR-05508000 Sao Paulo - Brazil

• Document type: Journal article
• Source: Hypertension; v. 62, n. 2, p. 263-273, AUG 2013.
• Web of Science Citations: 19

Abstract

Catecholaminergic C1 cells of the rostral ventrolateral medulla (RVLM) are key determinants of the sympathoexcitatory response to peripheral chemoreceptor activation. Overactivation of this reflex is thought to contribute to increased sympathetic activity and hypertension; however, molecular mechanisms linking peripheral chemoreceptor drive to hypertension remain poorly understood. We have recently determined that activation of P2Y1 receptors in the RVLM mimicked effects of peripheral chemoreceptor activation. Therefore, we hypothesize that P2Y1 receptors regulate peripheral chemoreceptor drive in this region. Here, we determine whether P2Y1 receptors are expressed by C1 neurons in the RVLM and contribute to peripheral chemoreceptor control of breathing, sympathetic activity, and blood pressure. We found that injection of a specific P2Y1 receptor agonist (MRS2365) into the RVLM of anesthetized adult rats increased phrenic nerve activity (approximate to 55%), sympathetic nerve activity (38 +/- 6%), and blood pressure (23 +/- 1 mmHg), whereas application of a specific P2Y1 receptor antagonist (MRS2179) decreased peripheral chemoreceptor-mediated activation of phrenic nerve activity, sympathetic nerve activity, and blood pressure. To establish that P2Y1 receptors are expressed by C1 cells, we determine in the brain slice preparation using cell-attached recording techniques that cells responsive to MRS2365 are immunoreactive for tyrosine hydroxylase (a marker of C1 cells), and we determine in vivo that C1-lesioned animals do not respond to RVLM injection of MRS2365. These data identify P2Y1 receptors as key determinants of peripheral chemoreceptor regulation of breathing, sympathetic nerve activity, and blood pressure. (AU)

• FAPESP's process: 10/19336-0 - Pontine mechanisms involved in cardiorespiratory control during central or peripheral chemoreceptors activation
• Grantee: Thiago dos Santos Moreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/09776-3 - Neural mechanisms involved in expiratory rhythm generator: possible involvement of the retrotrapezoid nucleus and the parafacial region
• Grantee: Ana Carolina Takakura Moreira
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 11/13462-7 - The interaction between retrotrapezoid nucleus astrocytes and neurons on respiratory responses promoted by central chemoreflex activation
• Grantee: Cleyton Roberto Sobrinho
• Support Opportunities: Scholarships in Brazil - Doctorate