Characterization of myocardium, isolated cardiomyocytes, and blood pressure in WKHA and WKY rats

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 similar to 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.