Contractile function of cardiomyocytes from the spontaneously hypertensive rat.
In essential hypertension it has been hypothesized that there is a generalized derangement in cellular Ca2+ homeostasis. The aim of this study was to assess whether there is functional evidence for increased vulnerability to Ca overload in cardiomyocytes derived from age-matched (11-week) normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rat (SHR) strains. Contraction cycles of isolated ventricular cardiomyocytes were recorded using a rapid digital imaging technique and were evaluated by computation of a range of normalized parameters. Significant differences in the basal contractile cycles of SHR and WKY ventricular cardiomyocytes recorded under control conditions (36 degrees C, 3 Hz, 1 mM Ca2+) were detected. SHR myocytes exhibited a reduction in maximum shortening attained (SHR/WKY = 0.79) and in maximum rates of shortening (SHR/WKY = 0.85) and lengthening (SHR/WKY = 0.87). In the SHR there was a small delay in excitation-contraction coupling latency and an abbreviation of the contractile cycle (SHR/WKY = 0.87). The time to peak contraction was not different in the two strains and was not altered by the inotropic interventions studied. No functional evidence for an increased susceptibility of the SHR myocytes to uncompensated "Ca2+ leakiness" was observed during repeated challenge of elevated extracellular Ca2+. In both strains, the relative increase in maximum shortening of myocytes to isoproterenol (10(-8) M) was similar, suggesting that differential sensitivity to adrenergic modulation is due to factors other than altered cardiomyocyte responsiveness. Diminished basal cardiomyocyte contractile function may represent an intrinsic feature of impaired cardiovascular function in this form of genetically determined hypertension.
Delbridge
L M
LM
Department of Physiology, University of Melbourne, Victoria, Australia.
Connell
P J
PJ
Morgan
T O
TO
Harris
P J
PJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D007545:Isoproterenol; D002118:Calcium