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1 Multidisciplinary Research Group in Hypertension, Institut de Recherches Cliniques de Montréal, Montreal, Quebec H2W 1R7; and 2 Division of Cardiology, Mount Sinai Hospital, University Health Network, Toronto, Ontario, Canada M5G 2C4
We previously reported that the
left ventricular (LV) mass of Wistar-Kyoto (WKY)-derived hyperactive
(WKHA) rats was higher than that of WKY rats in the absence of a
difference in systolic blood pressure. To extend these earlier
observations, we conducted a series of functional and morphological
investigations on both strains. Analysis of tissue sections revealed
that the surface of ventricular tissue from WKHA rats was higher than
that of WKY rats, without any enlargement of the cavity area. Analysis
of isolated adult cells showed that cell width (as well as cell volume) of ventricular cardiomyocytes was significantly higher in WKHA than WKY
rats. However, LV of WKHA rats contained ~33% less cardiomyocytes than those from WKY rats. Mean intracellular free calcium concentration of cardiomyocytes was also higher in WKHA than WKY rats. Hemodynamic measurements revealed that the values of the maximum rates of pressure
change (dP/dt) were higher in LV from WKHA rats. However, these differences were reduced (
dP/dt) or abolished
(+dP/dt) when the values were normalized for both the number
and mean cross-sectional area of ventricular cardiomyocytes. Mean
levels of systolic and diastolic blood pressure (corresponding to the
24-h average of measurements obtained continuously in conscious
unrestrained animals using radiotelemetric implants) were not
different between strains. However, circadian rhythm was more evident
in WKY rats, because the difference between morning and night values of
systolic and diastolic blood pressure was greater (by 3 mmHg) in WKY
rats. Altogether, our data validate the use of WKHA rats as models of predominantly concentric LV hypertrophy developing in the absence of
increased mean levels of hemodynamic cardiac load and show that the
hypertrophy phenotype is more pronounced in isolated cardiomyocytes
than at the level of the whole ventricle.
cell width; intracellular free calcium concentration; left ventricular hypertrophy; cardiac morphology; cardiac function
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