| dc.creator | Burgos, Juan Ignacio | |
| dc.creator | Yeves, Alejandra del Milagro | |
| dc.creator | Barrena, Jorge Pablo | |
| dc.creator | Portiansky, Enrique Leo | |
| dc.creator | Vila Petroff, Martín Gerardo | |
| dc.creator | Ennis, Irene Lucía | |
| dc.date | 2017 | |
| dc.date | 2020-11-04T18:46:14Z | |
| dc.date.accessioned | 2023-07-14T23:13:18Z | |
| dc.date.available | 2023-07-14T23:13:18Z | |
| dc.identifier | http://sedici.unlp.edu.ar/handle/10915/108322 | |
| dc.identifier | https://www.jmmc-online.com/article/S0022-2828(17)30292-4/fulltext | |
| dc.identifier | issn:0022-2828 | |
| dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/7449819 | |
| dc.description | Cardiac adaptation to endurance training includes improved contractility by a non-yet clarified mechanism. Since IGF-1 is the main mediator of the physiological response to exercise, we explored its effect on cardiac contractility and the putative involvement of nitric oxide (NO) and CaMKII in control and swim-trained mice.
IGF-1 increased cardiomyocyte shortening (128.1 ± 4.6% vs. basal; p ˂ 0.05) and accelerated relaxation (time to 50% relengthening: 49.2 ± 2.0% vs. basal; p ˂ 0.05), effects abrogated by inhibition of: AKT with MK-2206, NO production with the NO synthase (NOS) inhibitor L-NAME and the specific NOS1 inhibitor nitroguanidine (NG), and CaMKII with KN-93. In agreement, an increase in NO in response to IGF-1 (133.8 ± 2.2%) was detected and prevented by both L-NAME and NG but not KN-93, suggesting that CaMKII activation was downstream NO. In addition, we determined CaMKII activity (P-CaMKII) and phosphorylation of its target, Thr17-PLN. IGF-1, by a NO-dependent mechanism, significantly increased both (227.2 ± 29.4% and 145.3 ± 5.4%, respectively) while no changes in the CaMKII phosphorylation site of ryanodine receptor were evident. The improvement in contractility induced by IGF-1 was associated with increased Ca<sup>2+</sup> transient amplitude, rate of decay and SR content. Interestingly, this response was absent in cardiomyocytes from transgenic mice that express a CaMKII inhibitory peptide (AC3-I strain). Moreover, AC3-I mice subjected to swim training did develop physiological cardiac hypertrophy but not the contractile adaptation.
Therefore, we conclude that NO-dependent CaMKII activation plays a critical role in the improvement in contractility induced by IGF-1 and exercise training. Interestingly, this pathway would not contribute to the adaptive hypertrophy. | |
| dc.description | Facultad de Ciencias Médicas | |
| dc.description | Centro de Investigaciones Cardiovasculares | |
| dc.description | Facultad de Ciencias Veterinarias | |
| dc.format | application/pdf | |
| dc.format | 16-26 | |
| dc.language | en | |
| dc.rights | http://creativecommons.org/licenses/by-nc-sa/4.0/ | |
| dc.rights | Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) | |
| dc.subject | Ciencias Médicas | |
| dc.subject | Ciencias Veterinarias | |
| dc.subject | IGF-1, nitric oxide synthase 1 | |
| dc.subject | CaMKII | |
| dc.subject | cardiac contractility | |
| dc.subject | exercise training | |
| dc.title | Nitric oxide and CaMKII: Critical steps in the cardiac contractile response To IGF-1 and swim training | |
| dc.type | Articulo | |
| dc.type | Articulo | |
