Mechanisms Underlying the Increase in Force and Ca<sup>2+</sup> Transient That Follow Stretch of Cardiac Muscle : A Possible Explanation of the Anrep Effect
Myocardial stretch produces an increase in developed force (DF) that occurs in two phases: the first (rapidly occurring) is generally attributed to an increase in myofilament calcium responsiveness and the second (gradually developing) to an increase in [Ca<sup>2+</sup>]<sub>i</...
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| Autores principales: | , , , , |
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| Formato: | Articulo |
| Lenguaje: | Inglés |
| Publicado: |
1999
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| Materias: | |
| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/122777 |
| Aporte de: |
| Sumario: | Myocardial stretch produces an increase in developed force (DF) that occurs in two phases: the first (rapidly occurring) is generally attributed to an increase in myofilament calcium responsiveness and the second (gradually developing) to an increase in [Ca<sup>2+</sup>]<sub>i</sub>. Rat ventricular trabeculae were stretched from ≈88% to ≈98% of L<sub>max</sub>, and the second force phase was analyzed. Intracellular pH, [Na⁺]<sub>i</sub>, and Ca<sup>2+</sup> transients were measured by epifluorescence with BCECF-AM, SBFI-AM, and fura-2, respectively. After stretch, DF increased by 1.94±0.2 g/mm² (P<0.01, n=4), with the second phase accounting for 28±2% of the total increase (P<0.001, n=4). During this phase, SBFI<sub>340/380</sub> ratio increased from 0.73±0.01 to 0.76±0.01 (P<0.05, n=5) with an estimated [Na⁺]<sub>i</sub> rise of ≈6 mmol/L. [Ca<sup>2+</sup>]<sub>i</sub> transient, expressed as fura-2<sub>340/380</sub> ratio, increased by 9.2±3.6% (P<0.05, n=5). The increase in [Na⁺]<sub>i</sub> was blocked by 5-(N-ethyl-N-isopropyl)-amiloride (EIPA). The second phase in force and the increases in [Na⁺]<sub>i</sub> and [Ca<sup>2+</sup>]<sub>i</sub> transient were blunted by AT₁ or ET<sub>A</sub> blockade. Our data indicate that the second force phase and the increase in [Ca<sup>2+</sup>]<sub>i</sub> transient after stretch result from activation of the Na⁺/H⁺ exchanger (NHE) increasing [Na⁺]<sub>i</sub> and leading to a secondary increase in [Ca<sup>2+</sup>]<sub>i</sub> transient. This reflects an autocrine-paracrine mechanism whereby stretch triggers the release of angiotensin II, which in turn releases endothelin and activates the NHE through ET<sub>A</sub> receptors. |
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