The positive chronotropic effect of acetylcholine has muscarinic and nicotinic components in the neonatal rat heart.
Acetylcholine increases ventricular automaticity in neonatal but not adult canine Purkinje fibers. In this study, we used a rat model to investigate the mechanism for the increased automaticity, and used surface electrodes to record spontaneous rates from the ventricular septa of three different age groups: 1 to 2 days old (neonates), 6 to 9 days old (1 week old) and adults. Acetylcholine, 10(-12) and 10(-11) M, induced a significant increase in automaticity from a control of 103 +/- 6.5 beats per min to 117 +/- 9.0 and 118 +/- 10.8 beats per min, respectively, in the neonates (P less than .05). The increase was attenuated by atropine, 2 x 10(-6) M (P = .05), and eliminated by propranolol, 2 x 10(-7) M, or hexamethonium, 5 x 10(-6) M (P less than .05). In 1-week-old rats, acetylcholine, 10(-12) M, induced a lesser increase in automaticity from a control of 106 +/- 13.0 to 113 +/- 14.0 beats per min (P less than .05). The increase was blocked by atropine, 2 x 10(-6) M, propranolol, 2 x 10(-7) M, and by hexamethonium, 5 x 10(-6) M (all P less than .05). In adults, acetylcholine did not increase automaticity. Among the neonatal septa, 82% showed increased automaticity with acetylcholine alone, 78% showed increased automaticity in the presence of atropine and 13% showed increased automaticity in the presence of either propranolol or hexamethonium, suggesting a largely nicotinic mediated and catecholamine dependent component. In 1-week-old septa, 75% showed increased automaticity with acetylcholine alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Sun
L S
LS
Department of Pharmacology, Columbia University College of Physicians & Surgeons, New York, New York.
Roberts
L A
LA
Rosen
M R
MR
Robinson
R B
RB
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001285:Atropine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D006584:Hexamethonium Compounds / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013268:Stimulation, Chemical; D014439:Tyramine / Q000494:pharmacology
D006584:Hexamethonium Compounds; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D001285:Atropine; D011433:Propranolol; D000109:Acetylcholine; D014439:Tyramine