© 1999 American Heart Association, Inc.
Integrative Physiology |
Mechanisms Underlying the Increase in Force and Ca2+ Transient That Follow Stretch of Cardiac Muscle
A Possible Explanation of the Anrep Effect
From Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Argentina.
Correspondence to Dr Horacio E. Cingolani, Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Calle 60 y 120, 1900 La Plata, Argentina. E-mail cicme{at}atlas.med.unlp.edu.ar
Abstract—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 Lmax, 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, SBFI340/380 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-2340/380 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 ETA 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 ETA receptors.
Key Words: myocardial stretch • Ca2+ transient • Anrep effect • pHi • Na+/Ca2+ exchanger
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