HYPERTENSION--TRAINING-INDUCED INCREASE IN WORK CAPACITY

心脏继发于左心室（LV）肥大 肾血管性高血压（RVH）显示对 细胞外Ca 2+（Ca 2 +o）的正性肌力作用， 异速和等速自动调节。 这些内在功能 这些变化似乎与几种肌膜的变化同时发生， (SL)Ca 2+调节过程，包括缓慢Ca 2+减少 通道二氢吡啶结合位点和抑制SL ATP依赖性 Ca 2+泵活性本提案的主要目的是确定 耐力训练（i）可以恢复正常的Ca 2+依赖性自身调节 功能肥大的心脏和（ii）可以逆转SL的变化 由RVH产生的Ca 2+调节过程。 对这些 目的，RVH和LV肥大（HYP）将在雄性Fisher中产生 344只大鼠，采用Goldblatt，2肾-1夹手术。 心与世隔绝 从久坐的假手术对照组（S-SH），耐力训练的假手术， 手术对照组（T-SH）、左室肥厚大鼠（S-HYP）和训练组（T-SH）。 将研究患有LV HYP（T-HYP）的大鼠。 Ca 2 +-依赖性异时测量和 S-SH、T-SH、S-HYP和T-HYP心脏的等容自动调节功能 将使用分离的灌注工作心脏制备物进行评估。 [3 H] PN 200 -110与完整的杆状LV肌细胞的特异性结合， 富集的SL膜组分将提供缓慢的Ca 2+的估计值， S-SH、T-SH、S-HYP和t-HYP心脏中的通道数量。 的影响 训练和RVH对左心室肌膜ATP依赖性Ca ~（2+）泵活性的影响 将通过评估囊泡45 Ca 2+摄取来确定心肌 在高度富集的、由内而外的SL膜制备中。 的关系 在Ca 2+调节功能和Ca 2+依赖的SL标记物之间， 将检查离体工作心脏的功能性自动调节。 最后，这些体外变化对几个指数的可能影响 体内心血管功能的最大值将通过测量 S-SH、T-SH、S-HYP和T- HYP动物 几种耐力运动训练方式已被证明可以防止 和/或逆转LV HYP导致的心脏功能下降 继发于RVH。 更好地了解细胞变化 这些潜在的心脏功能的变化产生的训练， RVH，这些变化对完整动物的影响最终可能 证明在临床策略的发展，以防止 与高血压性心脏病相关的心肌功能障碍。

Hearts having undergone left ventricular (LV) hypertrophy secondary to renovascular hypertension (RVH) display a reduced responsiveness to the positive inotropic effects of extracellular Ca2+ (Ca2+o) during both heterometric and homeometric autoregulation. These intrinsic functional changes appear to occur concomitantly with changes in several sarcolemmal (SL) Ca2+ regulatory processes which include a reduction in slow Ca2+ channel dihydropyridine binding sites and a depression in SL ATP-dependent Ca2+ pump activity PRIMARY OBJECTIVES of this proposal are to determine if endurance training (i) can restore normal Ca2+o-dependent autoregulatory function to hypertrophied hearts and (ii) can reverse the changes in SL Ca2+ regulatory processes which are produced by RVH. Towards these objectives, RVH and LV hypertrophy (HYP) will be produced in male Fisher 344 rats using a Goldblatt, 2 kidney-1 clip procedure. Hearts isolated from sedentary sham-operated controls (S-SH), endurance trained sham- operated controls (T-SH), sedentary rats with LV HYP (S-HYP), and trained rats with LV HYP (T-HYP) will be studied. Ca2+o-dependent heterometric and homeometric autoregulatory function of S-SH, T-SH, S-HYP, and T-HYP hearts will be assessed using an isolated, perfused working heart preparation. The specific binding of [3H]PN200-110 to intact, rod-shaped LV myocytes and to enriched SL membrane fractions will provide an estimate of slow Ca2+ channel number in S-SH, T-SH, S-HYP, and t-HYP hearts. The effects of training and RVH on sarcolemmal ATP-dependent Ca2+ pump activity in LV myocardium will be determined via an assessment of vesicular 45Ca2+ uptake in a highly enriched, inside-out SL membrane preparation. The relationship between the SL markers of Ca2+ regulatory function and Ca2+o- dependent, functional autoregulation in isolated working hearts will be examined. Finally, the possible impact of these in vitro changes on several indices of cardiovascular function in vivo will be ascertained by measuring maximal cardiac output, stroke volume, and heart rate in S-SH, T-SH, S-HYP, and T- HYP animals. Several endurance exercise training modalities have been shown to prevent and/or reverse decrements in cardiac function that result from LV HYP secondary to RVH. A better understanding of the cellular changes underlying these alterations in cardiac function produced by training and RVH, and the impact of these changes on the intact animal may ultimately prove useful in the development of clinical strategies to prevent myocardial dysfunction associated with hypertensive heart disease.