Participação dos receptores purinérgicos P2 no núcleo do trato solitário sobre as respostas cardiorrespiratórias induzidas por hipóxia

Abstract

Cardiorespiratory responses to hypoxia are controlled by brainstem areas including the nucleus of the solitary tract (NTS). In the present study, we investigated the effects of suramin (a non-selective purinergic receptor antagonist), MRS 2179 (a selective P2Y1 purinergic receptor antagonist), PPADS (P2 purinergic receptor antagonist), alpha,beta-meATP (a selective P2X purinergic receptor agonist) and MRS 2365 (a selective P2Y1 purinergic receptor agonist) injected into the NTS on cardiorespiratory responses to hypoxia in conscious rats. Male Holtzman rats (290-310g, n=5-9/group) with stainless steel cannulas implanted into the NTS were used. We recording mean arterial pressure (MAP) and heart rate (HR) in conscious rats. Respiratory frequency (fR), tidal volume (Vt) and ventilation (VE) were recorded by whole-body plethysmography. VE, fR, Vt, MAP and HR were recorded in hypoxia (7% O2 for 35 min). Rats received bilateral injections of suramin (2 nmol/100 nL), MRS 2179 (1 nmol/100 nL), PPADS (2 nmol/100 nL), alpha,beta-meATP (2 nmol/100 nL), MRS 236 (1nmol/100 nL) or saline into the NTS 10 min before starting the hypoxia. Hypoxia reduced MAP (97 ± 3 mmHg, vs. normoxia: 119 ± 4 mmHg, p < 0.05) and increased HR (448 ± 17 bpm, vs. normoxia: 392 ± 18 bpm, p < 0.05) and VE (917 ±46 mL.min-1.Kg-1, vs. normoxia: 492 ±26 mL.min-1.Kg-1, p < 0.05). Bilateral injections of suramin into the NTS reduced Vt during hypoxia (7.1 ± 0.4 mL.Kg-1, vs. saline: 8.6 ± 0.5 mL.Kg-1, p = 0.046) resulting in a decrease in the hypoxia-induced hyperventilation (843 ± 66 mL.min-1.Kg-1, vs. saline: 1073 ± 98 mL.min-1.Kg-1, p = 0.05) without changing tachypnea induced by hypoxia (117 ± 3 breaths.min-1, vs. saline: 123 ± 6 breaths.min-1, p > 0.05), MAP (88 ± 5 mmHg, vs. saline: 94 ± 6 mmHg, p > 0.05) and HR (411 ± 19 bpm, vs. saline: 444 ± 20 bpm, p > 0.05). Furthermore, bilateral injections of MRS 2179 into the NTS reduced Vt during hypoxia (6.1 ± 0.5 mL.Kg-1, vs. saline: 7.4 ± 0.4 mL.Kg-1, p = 0.031) and hypoxia-induced hyperventilation (763 ± 77 mL.min-1.Kg-1, vs. saline: 917 ± mL.min-1.Kg-1, p = 0.043), without changing tachypnea (125 ± 10 breaths.min-1, vs. saline: 124 ± 4 breaths.min-1, p > 0.05), MAP (93 ± 1 mmHg, vs. saline: 97± 3 mmHg, p > 0.05) or HR (420 ± 23 bpm, vs. saline 448 ± 17 bpm, p > 0.05) during hypoxia. Bilateral injections of PPADS, alpha,beta meATP and MRS 2365 into the NTS did not change VE, MAP and HR on hypoxia condition. The present data show that P2 purinergic receptors, especially P2Y1, in the NTS are involved in the respiratory responses induced by hypoxia.