Activation of metabotropic glutamate receptor 1 inhibits chronic intermittent hypoxia-induced carotid body plasticity in rats / 生理学报

The purpose of the present study was to explore the role of carotid body metabotropic glutamate receptor 1 (mGluR1) in chronic intermittent hypoxia (CIH)-induced carotid body plasticity. Sprague Dawley (SD) rats were exposed to CIH (6%-21% O2, 4 min/cycle, 8 h/day) for 4 weeks. The blood pressure of rats was monitored non-invasively by tail-cuff method under consciousness. RT-qPCR was used to examine the mRNA expression level of mGluR1 in rat carotid body. Western blot was used to detect the protein expression level of mGluR1 in rat carotid body. The role of mGluR1 in CIH-induced carotid body sensory long-term facilitation (sLTF) was investigated by ex vivo carotid sinus nerve discharge recording, and the carotid body sLTF was evoked by a 10-episode of repetitive acute intermittent hypoxia (AIH: 1 min of 5% O2 interspersed with 5 min of 95% O2). The results showed that: 1) CIH increased the systolic blood pressure (P < 0.001), diastolic blood pressure (P < 0.005) and mean arterial blood pressure (P < 0.001) of rats; 2) CIH decreased the mRNA and protein levels of mGluR1 in the rat carotid body (P < 0.01); 3) 4 weeks of CIH induced carotid body sLTF significantly, exhibiting as an increasing baseline sensory activity during post-AIH, which was inhibited by application of an agonist of group I metabotropic glutamate receptors, (S)-3,5-dihydroxyphenylglycine (DHPG), during sLTF induction (P < 0.005). In summary, these results suggest that activation of mGluR1 inhibits CIH-induced carotid body plasticity in rats.

Role of group II and III mGluRs in carotid body plasticity induced by chronic intermittent hypoxia in rats / 生理学报

The aim of the present study was to explore the role of group II and III metabotropic glutamate receptors (mGluRs) in carotid body plasticity induced by chronic intermittent hypoxia (CIH) in rats. Sprague Dawley (SD) rats were treated with CIH in Oxycycler A84 hypoxic chamber for 4 weeks, and the tail artery blood pressure was measured at the end of model preparation. RT-qPCR was performed to examine the mRNA expression levels of mGluR2/3/8 in rat carotid body. Carotid sinus nerve activity was detected by ex vivo carotid sinus nerve discharge recording technique, and acute intermittent hypoxia (AIH) was administered to induce carotid body sensory long-term facilitation (sLTF), in order to observe the role of group II and group III mGluRs in carotid body plasticity induced by CIH. The results showed that: 1) After 4 weeks of CIH exposure, the blood pressure of rats increased significantly; 2) CIH down-regulated the mRNA levels of mGluR2/3, and up-regulated the mRNA level of mGluR8 in the carotid body; 3) AIH induced sLTF in carotid body of CIH group. In the CIH group, activation of group II mGluRs had no effect on sLTF of carotid body, while activation of group III mGluRs completely inhibited sLTF. These results suggest that CIH increases blood pressure in rats, and group III mGluRs play an inhibitory role in CIH-induced carotid body plasticity in rats.

Efectos del losartán sobre el glomus carotídeo en ratas normotensas adultas / Effects of losartan on the carotid glomus in adult normotensive rats

Recientemente comunicamos lesiones graves en el glomus carotídeo y los ganglios autonómicos de ratas SHR y sugerimos que este efecto se debía más al aumento de la presión arterial que al envejecimiento. Posteriormente demostramos, en SHR, que el ramipril, en comparación con el atenolol, ejerce un efecto protector sobre estas estructuras más allá de la reducción de la presión arterial. Teniendo en cuenta que no existen trabajos que describan los cambios que origina el bloqueo AT1 sobre la morfología del glomus en ratas normotensas, se realizó el presente estudio con el objetivo de evaluar el efecto del losartán sobre esta estructura de ratas Wistar macho tratadas durante 8 meses. Se emplearon 14 ratas de 4 semanas de edad, divididas en grupos control y losartán (10 mg/kg/día en el agua de bebida). La presión sistólica (PAS) se registró al inicio y luego mensualmente. A la edad de 9 meses se sacrificaron las ratas y se extrajeron los glomus carotídeos, se tiñeron con hematoxilina-eosina y tricrómico de Masson y se procesaron para histomorfometría con un analizador de imágenes. El grupo control registró una PAS de 115 ± 8,1, mientras que en el grupo losartán fue de105 ± 8,3 mm Hg (p = 0,0375). Histomorfométricamente, el grupo tratado mostró un área mayor del glomus con respecto al control (497.931 ± 48.783 versus 59.668 ± 6.196 µm2; p <0,0001) y una relación pared/luz en las arteriolas glómicas de 0,7 ± 0,1 versus 2,7 ± 0,6,respectivamente (p < 0,0001). El grupo control mostró disminución del área glómica y un aumento de la relación pared/luz, lo cual sugiere que la atrofia de las estructuras estudiadas a través del aumento de la edad se vincula con el aporte nutricio arterial.

Acetate enhances the chemosensory response to hypoxia in the cat carotid body in vitro in the absence of CO2-HCO3-

To determine if intracellular acidosis enhances hypoxic chemoreception in the absence of CO2-HCO3- at pH 7.4, the effects of sodium acetate (30 mM) were studied on the chemosensory responses of the cat carotid body to hypoxic, stagnant and cytotoxic hypoxia. Carotid bodies were perfused and superfused in vitro with Tyrode's solution, free of CO2-HCO3-, buffered with HEPES-NaOH, pH 7.40, at 36.5 +/d- 0.5 degrees C and equilibrated at PO2 of 125 Torr (perfusate) and < 20 Torr (superfusate). In the absence of acetate, hypoxia (PO2 25 Torr), flow interruption and NaCN (0.01-100 micrograms) augmented the chemosensory discharges. However, in the presence of acetate, the half-excitation time of these responses decreased and their amplitude increased. Thus, acetate enhances the chemosensory response to hypoxic, stagnant and cytotoxic hypoxia. It is suggested that that intracellular acidosis induced by acetate contributes to this potentiation by correcting the alkaline pHi caused by the absence of HCO3-(-)HCO2 in the perfusate