Respiratory effects of kynurenic acid microinjected into the ventromedullary surface of the rat

Several studies demonstrate that, within the ventral medullary surface (VMS), excitatory amino acids are necessary components of the neural circuits involved in the tonic and reflex control of respiration and circulation. In the present study we investigated the cardiorespiratory effects of unilateral microinjections of the broad spectrum glutamate antagonist kynurenic acid (2 nmol/200 nl) along the VMS of urethane-anesthetized rats. Within the VMS only one region was responsive to this drug. This area includes most of the intermediate respiratory area, partially overlapping the rostral ventrolateral medulla (IA/RVL). When microinjected into the IA/RVL, kynurenic acid produced a respiratory depression, without changes in mean arterial pressure or heart rate. The respiratory depression observed was characterized by a decrease in ventilation, tidal volume and mean inspiratory flow and an increase in respiratory frequency. Therefore, the observed respiratory depression was entirely due to a reduction in the inspiratory drive. Microinjections of vehicle (200 nl of saline) into this area produced no significant changes in breathing pattern, blood pressure or heart rate. Respiratory depression in response to the blockade of glutamatergic receptors inside the rostral VMS suggests that neurons at this site have an endogenous glutamatergic input controlling the respiratory cycle duration and the inspiratory drive transmission.

Cardiorespiratory alterations produced by pharmacological agents applied to the ventrolateral medulla (intermediate area) of the cat: effect of exercise condition on glycine-induced inhibition

1. To study the action of the intermediate area (IA), coextensive with the rostral ventrolateral medulla, on the neurophysiological mechanisms involved in the regulation of respiration, in terms of inspiratory drive and respiratory timing, cats were submitted to topical application of sodium pentobarbital (30 mg/ml), leptazol (200 mg/ml), glutamate (50 mg/ml) and glycine (100 and 50 mg/ml) to the IA. The effects of electrically induced exercise on the ventilatory response and oxygen uptake (VO2) obtained by topical application of glycine (50 mg/ml) to the IA were also studied. 2. Leptazol reduced minute ventilation (VE) and inspiratory drive (VT/TI) and changed the timing mechanism. Glutamate only increased tidal volume (VT), VE and VT/TI. Arterial blood pressure (AP) increased and heart rate (HR) did not change with either drug. 3. Sodium pentobarbital reduced VT and changed the timing mechanism. Glycine only reduced VE, VT and VT/TI. AP decreased and HR did not change with either drug. 4. The depressor effects of glycine on respiratory pattern, VO2 and CO2 production (VCO2) tended to be attenuated by exercise. 5. The fall in AP due to glycine application did not differ between resting and exercise conditions. 6. Our results indicate that at least two different nervous structures are involved in the IA: one responsible for the respiratory drive and sensitive to glycine and glutamate, and the other responsible for the regulation of the timing mechanism and sensitive to sodium pentobarbital and leptazol

Breathing pattern during pharmacological activation and blockade of the intermediate area of the ventrolateral surface of the cat medulla

The present study analyzes the respiratory pattern of chloralose- (50-60 mg/kg,iv) anesthetized cats treated with Nembutal (NE) (30 mg/ml), glycine (GL) (200 mg/ml) or leptazol (LE) (200 mg/ml) topically applied to the intermediate area of the ventrolateral surface of the medulla oblongata in a volume of 20 micronl. Application of NE and GL produced a decrease in ventilation (-24%) and tidal volume (-25%) suggesting that the intermediate area facilitates respiratory drive and inhibits the inspiratory off-switch mechanism. These results are consistent with the view that intermediate area is necessary for the central chemosensitivity to CO2. The topical application of LE produced an increase in inspiration time (12.5%), expiration time (20.8%) and tidal volume (7%). The increased tidal volume caused by LE is compatible with it action as a GL antagonist

Effect of exercise training during pregnancy: maternal and fetal responses of the rat

Pregnancy duration, offspring number, body weight gain per day, as well as offspring body and heart weights were studied in pregnant Wistar rats subjected to exercise training at relative work loads of 60, 70, 80 or 90% of maximum oxygen consumption (VO2max) (N = 6 for each group). Pregnancy duration, offspring number and heart weight of the rats subjected to exercise during pregnancy were not different from the control group not subjected to exercise training. Body weight gain per day of pregnant rats subjected to exercise was 4.64 + or - 0.21, 4.79 + or - 0.12 g, respectively, for work loads of 70,80 or 90% of VO2max. This decrease of body weight gain per day was ignificantly different (P<0.05) from the control group (5.69 + or - 0.22 g). The offspring body weight decreased in the rats submitted to work loads of 70,80 and 90% of VO2max(5.3-0 + or - 0.02 and 5.24 + or - 0.01g, respectively) by comparison to the control group value (5.73 + or - 0.07 g). These results suggest that only intense exercise could impair body weight gain in pregnant rats and their offspring