ALTERED CA2+ DYNAMICS IN SINGLE CARDIAC MYOCYTES FROM RENOVASCULAR HYPERTENSIVE RATS

Several functional and biochemical characteristics of hypertrophied hearts isolated from rats with renovascular hypertension provide indirect evidence that cellular Ca2+ dynamics during myocardial contraction-relaxation are altered. In this study, intracellular Ca2+ concentration ([Ca2+]i) dynamics were examined in paced left ventricular (LV) myocytes isolated from rats with hypertension (HYP) induced by partial occlusion of the left renal artery and from normotensive rats (Sham). Characteristic myocardial changes produced by renovascular hypertension included a 40% increase in LV weight and a 3.6-fold increase in the fractional expression of the beta-heavy chain of myosin in isolated LV myocytes. In periods of mechanical quiescence between contractions, basal [Ca2+]i values were similar in Sham and HYP LV myocytes. During a contraction-relaxation cycle in HYP myocytes, peak [Ca2+]i, +d[Ca2+]i/dt, and -d[Ca2+]i/dt were reduced, whereas the time required for [Ca2+]i to rise from a basal value to a peak value (time-to-peak [Ca2+]i) was unaffected. In both Sham and HYP myocytes, the fall in [Ca2+]i from peak to basal values could be approximated by a monoexponential rate constant, k(f). Values for k(f) were significantly smaller in HYP than in Sham myocytes. After treatment with 4-mu-M isoproterenol, peak [Ca2+]i, +[Ca2+]i/dt, -d[Ca2+]i/dt, and k(f) increased in both Sham and HYP myocytes. In contrast, basal [Ca2+]i and time-to-peak [Ca2+]i did not change. Thus, despite recent reports of inefficiencies of beta-adrenergic receptor coupling, there was no evidence of blunted beta-adrenergic responsiveness in HYP myocytes with respect to [Ca2+]i dynamics during contraction-relaxation. Finally, no Sham vs. HYP differences in the number of specific [H-3]-PN200-110 binding sites per cell in quiescent, rod-shaped myocytes were detected, but a significant reduction in [H-3]-PN200-110 binding sites in an enriched sarcolemmal membrane fraction isolated from HYP animals was observed. These observations are suggestive of a reduction in slow, Ca2+ channel surface density in HYP myocytes. The results of this study clearly indicate that [Ca2+]i dynamics during contraction-relaxation in single left ventricular myocytes are affected by residence in a chronic setting of renovascular hypertension. In addition, the prolonged [Ca2+]i removal phase observed in HYP myocytes can be restored toward normal by beta-adrenergic agonists.