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) Ra na catesbeiana was analyzed in situ (circulatory system intact) and in vitro (isolated heart or ventricular strip preparations). Topical app lication of ACh to the heart in situ resulted in a dose-dependent decr ease in heart rate and in a slight decrease in systolic ventricular pr essure in all developmental stages. Injection of acetylcholine into th e ventricle lumen in situ caused a dose-dependent transient decrease i n systolic ventricular pressure, with little heart rate effect. Intrav entricular ACh injection also changed the hemodynamic coupling between ventricle and conus arteriosus, generating a biphasic pressure profil e in the conus due to sequential contractions of the ventricle and of the conus. In situ the sensitivity of the ventricle to ACh decreased d uring larval development, with the lowest sensitivity in small postmet amorphic adults. ACh applied in vitro to cardiac muscle strips or smal l hearts produced a negative inotropic effect, The ACh dose necessary to induce a 50% reduction in muscle strip contraction force in vitro d ecreased substantially during larval development, indicating an increa se in ACh sensitivity with development. The effects of ACh both in vit ro and in situ were diminished or eliminated by topical application or injection of atropine, suggesting the presence of muscarinic choliner gic receptors. After preincubation with the acetylcholinesterase block er eserine, injection of ACh into the conus arteriosus decreased systo lic ventricular pressure with a delay of 4-10 seconds, probably repres enting 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 cardia c pacemaker, mainly influencing heart rate. These responses occur as e arly as TK, stage II, indicating a well-developed set of mechanisms to regulate cardiovascular performance early in development. (C) 1993 Wi ley-Liss, Inc.