cycling during compensated hypertrophy in SHR is a decrease in NCX activity in subepicardial cells; this increases SR Ca 2ϩ content and hence Ca 2ϩ transient amplitude, thus helping to maintain the strength of contraction in the face of an increased afterload. cardiac myocytes; epicardium; endocardium; sarcoplasmic reticulum; t tubules; spontaneously hypertensive rats SYSTEMIC HYPERTENSION IS ASSOCIATED with cardiac morbidity and death (7); the increased afterload imposed on the heart by hypertension results in cardiac hypertrophy, which predisposes to heart failure. Such pressure overload leads to concentric hypertrophy, characterized by an increase in cell size and ventricular wall thickness. Remodeling also results in altered excitation-contraction coupling. In the spontaneously hypertensive rat (SHR), a genetic model of hypertension and cardiac hypertrophy (11, 13), this is characterized by maintained or enhanced systolic Ca 2ϩ transient and contraction amplitude and a slowed time course of contraction and relaxation (4,5,20,30).A number of changes in the excitation-contraction coupling pathway have been identified that may account for the altered Ca 2ϩ transient and contraction, including action potential prolongation, increased sarcoplasmic reticulum (SR) Ca 2ϩ content (5), and larger amplitude Ca 2ϩ sparks (30). However, the mechanisms underlying the changes in Ca 2ϩ transient configuration are still not well understood. In many studies, an increase in Na ϩ /Ca 2ϩ exchange (NCX) expression has been reported during compensated hypertrophy, although, paradoxically, function often appears downregulated or unaltered. For example in the mouse, after surgically induced pressure overload, NCX transcript and protein expression increase but caffeine-evoked inward current and Ni 2ϩ -sensitive current decrease (34). Similarly, in another mouse model of compensated hypertrophy, NCX, SR Ca 2ϩ -ATPase (SERCA), and phospholamban protein levels increase, but NCX current is not significantly altered (16); in addition, in the SHR during compensated hypertrophy, expression of phospholamban, SERCA, and ryanodine receptor are unchanged (30). In contrast, in hypertrophied canine myocytes, Ca 2ϩ extrusion via NCX and Ni 2ϩ -sensitive current are increased (31). Thus there appear to be differences that may be due to the model and to the degree of progression of hypertrophy. In addition, the ventricular myocardium displays regional variations in its structural, mechanical, and electrical properties in normal and hypertrophied hearts (6,20,22,23), probably in part as a result of regional differences in wall stress (25). Recent work in the SHR has shown that the amplitude and time course of the action potential, Ca 2ϩ transient, and contraction are altered differentially in subepicardial (Epi) and subendocardial (Endo) myocytes during compensated hypertrophy (20). However, the mechanisms underlying these regional changes in the Ca 2ϩ transient have not been investigated. The present study was designed, therefore, to investigate the...

These data show that both isoflurane and sevoflurane reduce apparent myofilament Ca(2+) sensitivity at steady state. However, sevoflurane (but not isoflurane) induced transient changes in apparent myofilament Ca(2+) sensitivity, which would contribute to its inotropic profile.

Alfentanil, at concentrations achieved in clinical practice, increased contraction in ventricular cells by a mechanism involving an increase in the sensitivity of the contractile apparatus to Ca(2+).

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Application of halothane and removal of sevoflurane sensitize the SR Ca(2+) release process (and vice versa on removal). Sevoflurane reversed the effects of halothane, suggesting they may act at the same subcellular target on the SR.