Key result
Acetylcholine induces dose-dependent decreases in heart rate and ventricular pressure across amphibian developmental stages.
Why the study?
The developmental changes in acetylcholine influence on cardiac performance in Rana catesbeiana were not fully characterized in situ and in vitro.
Extends cholinergic cardiac regulation across anuran development; leaves open translation to mammals or clinical practice.
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 in to 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 in to the conus arteriosus decreased systolic ventricular pressure with a delay of 4–10 seconds, probably representing the minimum blood circulation time. The observed inotropic and chronotropic responses result from the action of ACh on cardiac muscle, primarily affecting systolic ventricular pressure, and on the cardiac pacemaker, mainly influencing heart rate. These responses occur as early as TK, stage II, indicating a well‐developed set of mechanisms to regulate cardiovascular performance early in development.
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Pelster et al. (1993) studied this question. Acetylcholine (ACh) was evaluated on Cardiac performance (heart rate and systolic ventricular pressure). Application of acetylcholine produced dose-dependent decreases in heart rate and systolic ventricular pressure in both larval and postmetamorphic Rana catesbeiana.