ACTIVATION OF CENTRAL MUSCARINIC RECEPTORS CAUSES RESPIRATORY STIMULATION IN CONSCIOUS ANIMALS

Oxotremorine (10 μg/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 kPa within 15 min. Blood pH fell from 7.44 to 7.16. Blood pressure increased by 11.6%, 5 min after oxotremorine injection. The acidosis was shown to be due to an increase in blood lactic acid from 41 to 132 mg/100 ml. 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. It is suggested that the lactic acidosis induced by oxotremorine results from stimulation of β‐adrenoceptors in skeletal muscle by catecholamines released from the adrenal medulla and sympathetic nerves. 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. 1981 British Pharmacological Society