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

Autor(es)

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

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Hypertension; v. 62, n. 2, p. 263-273, AUG 2013.
• Citações Web of Science: 19

Resumo

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)

• Processo FAPESP: 10/19336-0 - Mecanismos pontinos envolvidos no controle cardiorrespiratório durante a ativação dos quimiorreceptores centrais ou periféricos
• Beneficiário: Thiago dos Santos Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/09776-3 - Mecanismos neurais envolvidos na geração do ritmo expiratório: possível envolvimento do núcleo retrotrapezoide e da região parafacial
• Beneficiário: Ana Carolina Takakura Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 11/13462-7 - Interação entre astrócitos e neurônios do núcleo retrotrapezóide nas respostas respiratórias promovidas pela ativação do quimiorreflexo central
• Beneficiário: Cleyton Roberto Sobrinho
• Modalidade de apoio: Bolsas no Brasil - Doutorado