Mechanisms Underlying the Increase in Force and Ca²⁺ Transient That Follow Stretch of Cardiac Muscle : A Possible Explanation of the Anrep Effect

• Autores: Álvarez, Bernardo Víctor; Pérez, Néstor Gustavo; Ennis, Irene Lucía; Camilión de Hurtado, María Cristina; Cingolani, Horacio Eugenio
• Año de publicación: 1999
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Medicina; myocardial stretch; Ca2+; transient; Anrep effect; pHi; Na+/Ca2+ exchanger
• Institución: Universidad Nacional de La Plata

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 [Ca²⁺]_i. Rat ventricular trabeculae were stretched from ≈88% to ≈98% of L_max, and the second force phase was analyzed. Intracellular pH, [Na⁺]_i, and Ca²⁺ 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_340/380 ratio increased from 0.73±0.01 to 0.76±0.01 (P<0.05, n=5) with an estimated [Na⁺]_i rise of ≈6 mmol/L. [Ca²⁺]_i transient, expressed as fura-2_340/380 ratio, increased by 9.2±3.6% (P<0.05, n=5). The increase in [Na⁺]_i was blocked by 5-(N-ethyl-N-isopropyl)-amiloride (EIPA). The second phase in force and the increases in [Na⁺]_i and [Ca²⁺]_i transient were blunted by AT₁ or ET_A blockade. Our data indicate that the second force phase and the increase in [Ca²⁺]_i transient after stretch result from activation of the Na⁺/H⁺ exchanger (NHE) increasing [Na⁺]_i and leading to a secondary increase in [Ca²⁺]_i 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_A receptors.
Facultad de Ciencias Médicas
Centro de Investigaciones Cardiovasculares