An excitatory amino acid(s) in the ventrolateral medulla is (are) required for breathing to occur in the anesthetized cat.

The purpose of the present study was to identify sites(s) in the ventrolateral medulla where excitatory amino acids are involved in respiratory control. For this purpose, the respiratory effects produced by bilateral microinjection of excitatory amino acid antagonist drugs were examined while tidal volume (Vt), respiratory rate (f), arterial blood pressure and heart rate were monitored in chloralose-anesthetized cats. Microinjection of kynurenic acid (12.5 nmol) into a site approximately 3 mm rostral to obex, 4 mm lateral to midline and 1.5 mm below the ventral surface produced a decrease in Vt (-20 +/- 2 ml), an increase in f (+20 +/- 3 breaths/min) and a decrease in respiratory minute volume (-108 +/- 19 ml/min) (n = 8). These changes progressed to apnea in each animal tested. No significant changes in blood pressure or heart rate were observed. To determine the excitatory amino acid receptor subtype(s) involved, antagonists of n-methyl-D-aspartate (NMDA) (3-[(RS)-carboxypiperazin-4-yl]-propyl-1-phosphoric acid (CPP] and non-NMDA [6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)] receptors were microinjected bilaterally into this site. In the case of CPP, three doses were studied (0.25 nmol, n = 4; 0.75 nmol, n = 3; 2.25 nmol, n = 2). All three doses produced similar decreases in Vt (-12 +/- 1, P less than .05; -10 +/- 1, P less than .05; and -16 +/- 5 ml, respectively) and increases in f (+14 +/- 2, P less than .05; +10 +/- 3, P less than .05; and +12 +/- 3 breaths/min, respectively). None of these animals exhibited apnea.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiorespiratory effects produced by activation of cholinergic muscarinic receptors on the ventral surface of the medulla.

Our purpose was to examine the influence of inhibition of cholinesterase at the ventral surface of the medulla on cardiorespiratory activity in the chloralose-anesthetized cat. Administration of the anticholinesterase agent, diisopropylfluorophosphate (DFP) to areas responding to acetylcholine (i.e., rostral and caudal chemosensitive areas of the ventral surface of the medulla) in doses ranging from 12.5 to 50 micrograms bilaterally had minimal effects on cardiorespiratory activity. However, similar doses applied to the intermediate area of the ventral surface of the medulla produced an increase in tidal volume and hypotension. For example, a dose of 12.5 micrograms increased tidal volume by 14 +/- 3 ml (P greater than .05). Similar responses were seen with higher doses of DFP; in addition, respiratory depression (apnea) also occurred. This depression was characterized by a slowing in respiratory rate. The organophosphate compound, soman, in doses of 0.25 and 0.5 micrograms produced effects similar to those seen with DFP with the exception that an increase in respiratory rate was observed before the decrease in respiratory rate occurred. In addition, a greater degree of hypotension was observed with soman as compared to DFP. Findings comparable to those obtained with DFP were produced by the muscarinic receptor agonist, oxotremorine (0.077-10 micrograms). The effects of DFP, soman and oxotremorine were counteracted by locally applied atropine. In addition, measurements of acetylcholinesterase activity taken from the rostral, intermediate and caudal areas indicate a relatively low activity at the rostral area but a relatively high activity at the intermediate area.(ABSTRACT TRUNCATED AT 250 WORDS)