In pithed normotensive rats
muscarinic receptors were characterized in heart, urinary bladder and sympathetic ganglia; the selectivity of some classical
muscarinic agents for these subtypes was investigated. The potencies in decreasing heart rate, increasing bladder pressure and increasing diastolic blood pressure were measured for the following, intraarterially administered
cholinergic agonists:
McN-A-343 ([4-m-chlorophenylcarbamoyloxy]-2-butynyltrimethylammonium),
pilocarpine,
carbachol,
oxotremorine,
arecoline,
acetyl-beta-methylcholine and
acetylcholine. The selective M1-antagonist
pirenzepine, the mixed M1/M2-antagonist
dexetimide and the cardioselective M2-antagonist
gallamine were used as tools for identification of the receptors. All data were obtained after intravenous pretreatment with a high dose of
atenolol to eliminate
tachycardia induced by stimulating sympathetic ganglionic
muscarinic receptors.
Dexetimide strongly antagonized the
bradycardia as well as the increase in bladder pressure induced by
pilocarpine,
carbachol,
oxotremorine,
arecoline,
acetyl-beta-methylcholine and
acetylcholine, whereas
pirenzepine was much less effective.
Gallamine antagonized the
bradycardia, whereas no influence was found on the bladder contraction.
Pilocarpine acted as a partial agonist in reducing heart rate as well as in increasing bladder pressure, whereas
McN-A-343 was almost ineffective in doses up to 1 mg/kg. The hypertensive response to
pilocarpine and
carbachol was less pronounced than that produced by
McN-A-343.
Pirenzepine and
dexetimide significantly antagonized the hypertensive response to
McN-A-343 and
pilocarpine, whereas
gallamine was much less effective. The hypertensive response induced by
carbachol was totally blocked by
hexamethonium. The other agonists used in this study did not produce a significant increase in diastolic blood pressure in doses that produced a maximal effect on heart rate and urinary bladder pressure.(ABSTRACT TRUNCATED AT 250 WORDS)