Developmental changes in the acetylcholine influence on heart muscle of Rana catesbeiana: in situ and in vitro effects.

The influence of acetylcholine (ACh) on cardiac performance of larval (Taylor Kollros [TK] stages II-XVIII) and postmetamorphic (3-609 g) Rana catesbeiana was analyzed in situ (circulatory system intact) and in vitro (isolated heart or ventricular strip preparations). Topical application of ACh to the heart in situ resulted in a dose-dependent decrease in heart rate and in a slight decrease in systolic ventricular pressure in all developmental stages. Injection of acetylcholine into the ventricle lumen in situ caused a dose-dependent transient decrease in systolic ventricular pressure, with little heart rate effect. Intraventricular ACh injection also changed the hemodynamic coupling between ventricle and conus arteriosus, generating a biphasic pressure profile in the conus due to sequential contractions of the ventricle and of the conus. In situ the sensitivity of the ventricle to ACh decreased during larval development, with the lowest sensitivity in small postmetamorphic adults. ACh applied in vitro to cardiac muscle strips or small hearts produced a negative inotropic effect. The ACh dose necessary to induce a 50% reduction in muscle strip contraction force in vitro decreased substantially during larval development, indicating an increase in ACh sensitivity with development. The effects of ACh both in vitro and in situ were diminished or eliminated by topical application or injection of atropine, suggesting the presence of muscarinic cholinergic receptors. After preincubation with the acetylcholinesterase blocker eserine, injection of ACh into the conus arteriosus decreased systolic ventricular pressure with a delay of 4-10 seconds, probably representing the minimum blood circulation time.(ABSTRACT TRUNCATED AT 250 WORDS)