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)
Gillis
R A
RA
Department of Pharmacology, Georgetown University, School of Medicine, Washington, District of Columbia.
Walton
D P
DP
Quest
J A
JA
Namath
I J
IJ
Hamosh
P
P
Dretchen
K L
KL
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D002415:Cats; D002802:Cholinesterases / Q000378:metabolism; D005260:Female; D007022:Hypotension / Q000139:chemically induced; D007531:Isoflurophate / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000201:enzymology / Q000378:metabolism*; D010095:Oxotremorine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000502:physiology*; D012119:Respiration / Q000187:drug effects*; D013990:Tidal Volume
D011976:Receptors, Muscarinic; D007531:Isoflurophate; D010095:Oxotremorine; D002802:Cholinesterases; D000109:Acetylcholine