Cardiomyocyte function associated with hyperactivity and/or hypertension in genetic models of LV hypertrophy

1 Department of Molecular Physiology and Biophysics, 2 Department of Medicine, University of Vermont, Burlington, Vermont 05405 Submitted 29 March 2005 ; accepted in final form 8 September 2005 We examined cardiomyocyte intracellular calcium ([Ca 2+ ] i ) dynamics and sarcomere shortening dynamics in genetic rat models of left ventricular (LV) hypertrophy associated with or without hypertension (HT) and with or without hyperactive (HA) behavior. Previous selective breeding of the spontaneously hypertensive rat (SHR) strain, which is HA and HT, with the Wistar-Kyoto (WKY) rat strain, which is not hyperactive (NA) and not hypertensive (NT), has led to two unique strains: the WKHA strain, selected for HA and NT, and the WKHT strain, selected for NA and HT. Cardiomyocytes were isolated from young adult males and females of each strain, paced at 2, 3, and 4 Hz in 1.2 mM external Ca 2+ concentration at 37°C, and cardiomyocyte [Ca 2+ ] i and sarcomere dynamics were recorded simultaneously. Under these conditions, LV cardiomyocyte systolic and diastolic [Ca 2+ ] i dynamics and diastolic sarcomere dynamics in the WKHT were significantly enhanced compared with WKY controls, suggesting an underlying LV hypertrophic response that successfully compensated for HT in the absence of HA. LV cardiomyocyte [Ca 2+ ] i dynamics in the WKHA and SHR were strikingly similar to each other and only slightly reduced compared with WKY. LV cardiomyocyte systolic and diastolic sarcomere dynamics, on the other hand, were significantly reduced in the SHR compare with WKHA and more so in male than in female SHR. We conclude from these data that HT alone is an insufficient descriptor of the cause of LV hypertrophy and diminished LV cardiomyocyte function in the SHR rat. These data further suggest that HA (augmented by male sex) in the SHR may interact with the HT state to initiate impaired cardiomyocyte function and thereby inhibit or undermine an otherwise compensatory response that may occur with HT in the absence of HA. spontaneously hypertensive rat; Wistar-Kyoto rat; Wistar-Kyoto hypertensive; Wistar-Kyoto hyperactive; fura-2; left ventricular Address for reprint requests and other correspondence: B. M. Palmer, 127 HSRF-Beaumont Ave., Dept. of Molecular Physiology and Biophysics, Univ. of Vermont, Burlington, VT 05405 (email: palmer{at}physiology.med.uvm.edu )