Activation of central muscarinic receptors causes respiratory stimulation in conscious animals.
1 Oxotremorine (10 microgram/kg) injected intravenously into conscious rabbits pretreated with atropine-methyl-nitrate (ATMN, 0.5 mg/kg) caused significant increases in respiration rate from 94 to 131 per min, and in PaO2 from 13.8 to 15.4 kPa, and a decrease in PaCO2 from 3.30 to 2.09 pKa within 15 min. Blood pH fell from 7.44 to 7.16. 2 Blood pressure increased by 11.6%, 5 min after oxotremorine injection. 3 The acidosis was shown to be due to an increase in blood lactic acid from 41 to 132 mg/100 ml. 4 Pretreatment with propranolol (5 mg/kg s.c.) prevented the lactic acidosis and fall in pH but did not alter the respiratory stimulation induced by oxotremorine. 5 It is suggested that the lactic acidosis induced by oxotremorine results from stimulation of beta-adrenoceptors in skeletal muscle by catecholamines released from the adrenal medulla and sympathetic nerves. 6 Since all the above effects of oxotremorine are antagonized by hyoscine (5 mg/kg) but not by ATMN (0.5 mg/kg), it is concluded that oxotremorine can stimulate respiration by a direct action on muscarinic receptors in the central nervous system.
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D010095:Oxotremorine / Q000494:pharmacology*; D011817:Rabbits; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012119:Respiration / Q000187:drug effects*
D002395:Catecholamines; D007773:Lactates; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D019344:Lactic Acid; D010095:Oxotremorine