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1 Department of Physiology, Loyola University Chicago, Maywood, Illinois 60153; and 2 Medizinische Klinik III, Universität Freiburg, 79106 Freiburg, Germany
To study the effect of left ventricular (LV)
hypertrophy on force and Ca2+
handling in isolated rat myocardium, LV hypertrophy was induced in rats
by banding of the abdominal aorta. After 16 wk, arterial pressure was
assessed by catheterization. LV trabeculae were isolated and loaded
with indo 1 salt by iontophoretic injection. Isometric force and
intracellular free Ca2+
concentration
([Ca2+]i)
were measured at stimulation frequencies between 0.25 and 3 Hz and rest
intervals between 2 and 240 s. Sarcoplasmic reticulum (SR)
Ca2+ content was also investigated
using rapid cooling contractures (RCC). Systolic and diastolic pressure
as well as heart weight-to-body weight ratios were significantly
elevated in banded compared with control animals (167 vs. 117 mmHg, 108 vs. 83 mmHg, and 4.6 vs. 4.0 mg/g, respectively). At high frequencies,
twitch relaxation and
[Ca2+]i
decline rates were significantly slower in banded compared with control
rats, and diastolic
[Ca2+]i
was higher in the banded rat muscles (at 3 Hz, force half-time = 83 vs.
68 ms; time constant of
[Ca2+]i
decline = 208 vs. 118 ms; and diastolic
[Ca2+]i = 505 vs. 353 nM). These differences could not be ascribed to altered
Na+/Ca2+
exchange, since twitch relaxation and
Ca2+ handling were not different
between groups in the presence of caffeine (or cyclopiazonic acid plus
ryanodine), where relaxation depends primarily on
Na+/Ca2+
exchange. After long rest intervals (
120 s), control rats showed a
significant rest potentiation of force and
Ca2+ transients, whereas banded
rats did not. In addition, RCC amplitudes increased with rest in
control but were unaltered in banded rats. In summary,
pressure-overload hypertrophy was associated with slower twitch
relaxation and
[Ca2+]i
decline but also with blunted rest potentiation of twitches and SR
Ca2+ content of LV trabeculae. The
decrease in SR Ca2+-ATPase
function in banded rats may contribute to the observed diastolic
dysfunction associated with pressure-overload hypertrophy.
systemic hypertension; iontophoretic injection; rapid cooling contractures; force-frequency relationship; postrest relationship
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