Bv. Alvarez et al., Mechanisms underlying the increase in force and Ca2+ transient that followstretch of cardiac muscle - A possible explanation of the Anrep effect, CIRCUL RES, 85(8), 1999, pp. 716-722
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 d
eveloping) to an increase in [Ca2+](i). Rat ventricular trabeculae were str
etched from approximate to 88% to approximate to 98% of L-max, and the seco
nd force phase was analyzed. Intracellular pH, [Na+](i), and Ca2+ transient
s were measured by epifluorescence with BCECIF-AM, SBFI-AM, and fura-2, res
pectively. After stretch, DF increased by 1.94+/-0.2 g/mm(2) (P<0.01, n=4),
with the second phase accounting for 28+/-2% of the total increase (P<0.00
1, 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 approximate t
o 6 mmol/L. [Ca2+](i) transient, expressed as fura-2(340/380) ratio, increa
sed 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 i
ncreases in [Na+](i) and [Ca2+](i) transient were blunted by AT(1) or ETA b
lockade. Our data indicate that the second force phase and the increase in
[Ca2+](i) transient after stretch result from activation of the Na+/H+ exch
anger (NHE) increasing [Na+](i) and lending to a secondary increase in [Ca2
+](i) transient. This reflects an autocrine-paracrine mechanism whereby str
etch triggers the release of angiotensin II, which in turn releases endothe
lin and activates the NHE through ETA receptors.