Hypertension, Vol 24, 347-356, Copyright © 1994 by American Heart Association
WW Brooks, OH Bing, SE Litwin, CH Conrad and JP Morgan
We studied functional and intracellular calcium responses to treppe and
extracellular calcium in spontaneously hypertensive rat (SHR) hearts during
the transition from compensated pressure overload to failure. Intracellular
calcium was measured using aequorin, a bioluminescent Ca2+ indicator.
Experiments were performed with intact, isovolumically contracting,
buffer-perfused hearts from three rat groups: (1) aging SHR with evidence
of heart failure (SHR-F), (2) age-matched SHR with no evidence of heart
failure (SHR-NF), and (3) age-matched normotensive Wistar-Kyoto (WKY) rats.
In each experiment, left ventricular pressure and intracellular calcium
transients were simultaneously recorded. Hearts were studied at 30 degrees
C and paced at a rate of 1.6 Hz while being perfused with oxygenated
Krebs-Henseleit solution (95% O2/5% CO2) at 100 mm Hg. At the baseline
state, peak systolic pressure was greatest in the SHR-NF group and lowest
in the SHR-F group. Peak and resting [Ca2+]i were not significantly
different among groups; however, the calcium transient was prolonged in the
SHR-NF and SHR-F groups. With increasing perfusate [Ca2+]o from 0.5 to 3.0
mmol/L, the relative increases in peak [Ca2+]i and peak systolic pressure
were similar among groups. When stimulation rate was increased from 1.6 to
2.0, 2.4, 2.8, and 3.2 Hz, peak [Ca2+]i, peak systolic pressure, and +/-
dP/dt fell in SHR-F hearts. Peak systolic pressure decreased in the SHR-NF
group at rates above 2.4 Hz but did not decline in the WKY group. Peak
[Ca2+]i increased in the WKY and SHR-NF groups with increasing heart rates.
Peak systolic pressure did not fall significantly in the WKY group at any
heart rate. Elevation of diastolic [Ca2+]i and/or calcium transient and
pressure alternans were present in 8 of 13 SHR-F hearts at the highest
stimulation rate, findings that were absent in both the WKY and SHR-NF
hearts. We conclude the following: (1) Under baseline conditions, depressed
contractile function of failing myocardium cannot be explained by decreased
peak [Ca2+]i, (2) relative increases in [Ca2+]i and inotropy with
increasing [Ca2+]o are proportional among groups; and (3) although peak
systolic [Ca2+]i and inotropy are maintained with increasing stimulation
rate in the WKY and SHR-NF groups, peak systolic [Ca2+]i and pressure
decrease in parallel in the SHR-F heart with increasing stimulation rate,
suggesting that impaired calcium cycling may contribute to compromised pump
function in the SHR- F heart.
ARTICLES
Effects of treppe and calcium on intracellular calcium and function in the failing heart from the spontaneously hypertensive rat
Department of Veterans Affairs Medical Center, Boston, Mass.
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