Kolwicz Stephen C, Kubo Hajime, MacDonnell Scott M, Houser Steven R, Libonati Joseph R
Department of Kinesiology, Temple Univ., Philadelphia, PA, USA.
J Appl Physiol (1985). 2007 Feb;102(2):628-33. doi: 10.1152/japplphysiol.00449.2006. Epub 2006 Nov 2.
Beta-adrenergic receptor (beta-AR) responsiveness is downregulated in left ventricular (LV) hypertrophy induced by chronic hypertension. While exercise training in hypertension enhances beta-AR responsiveness, the role of adenylyl cyclase remains unclear. The purpose of the present study was to test whether treadmill running in the spontaneously hypertensive rat (SHR) model improves LV responsiveness to forskolin (FOR) or the combination of FOR + isoproterenol (FOR+ISO). Female SHR (16-wk) were randomly placed into sedentary (SHR-SED; n = 7) or treadmill-trained (SHR-TRD; n = 8) groups. Wistar-Kyoto (WKY; n = 7) animals acted as normotensive controls. Langendorff, isovolumic LV performance was established at baseline and during incremental FOR infusion (1 and 5 micromol/l) and FOR+ISO (5 micromol/l + 1x10(-8) mol/l). Heart rate, systolic blood pressure, and heart-to-body weight ratio were lower in WKY relative to both SHR groups (P < 0.05). LV performance and heart rate significantly increased in all groups to a similar extent with incremental FOR infusion. However, in the presence of 5 micromol/l FOR, ISO increased LV developed pressure, positive change in LV pressure, and negative change in LV pressure to a greater extent in SHR-TRD relative to SHR-SED (P < 0.05). Phospholamban phosphorylation at the Thr17 was greater in SHR-TRD relative to SHR-SED and WKY (P < 0.05). Absolute LV developed pressure was moderately correlated with phospholamban phosphorylation at both the Ser16 (r = 0.64; P < 0.05) and Thr17 (r = 0.52; P < 0.05). Our data suggest that the adenylyl cyclase step in the beta-AR cascade is not downregulated in the early course of hypertension and that the enhanced beta-AR responsiveness with training is likely mediated at levels other than adenylyl cyclase. Our data also suggest that beta-AR inotropic responsiveness in the presence of direct adenylyl cyclase agonism is improved in trained compared with sedentary SHR hearts.
在慢性高血压所致左心室肥厚中，β-肾上腺素能受体（β-AR）反应性下调。虽然高血压患者进行运动训练可增强β-AR反应性，但腺苷酸环化酶的作用仍不清楚。本研究旨在测试在自发性高血压大鼠（SHR）模型中进行跑步机跑步是否能改善左心室对福斯高林（FOR）或FOR+异丙肾上腺素（FOR+ISO）组合的反应性。将16周龄雌性SHR随机分为久坐组（SHR-SED；n = 7）或跑步机训练组（SHR-TRD；n = 8）。Wistar-Kyoto（WKY；n = 7）动物作为正常血压对照。采用Langendorff法，在基线以及递增输注FOR（1和5 μmol/l）和FOR+ISO（5 μmol/l + 1×10⁻⁸ mol/l）期间测定左心室等容性能。相对于两个SHR组，WKY的心率、收缩压和心体比更低（P < 0.05）。随着FOR递增输注，所有组的左心室性能和心率均显著增加，且增加程度相似。然而，在存在5 μmol/l FOR的情况下，相对于SHR-SED，ISO在SHR-TRD中使左心室舒张末压、左心室压力正变化和左心室压力负变化增加的程度更大（P < 0.05）。相对于SHR-SED和WKY，SHR-TRD中磷酸受磷蛋白在Thr17位点磷酸化程度更高（P < 0.05）。左心室舒张末压绝对值与磷酸受磷蛋白在Ser16（r = 0.64；P < 0.05）和Thr17（r = 0.52；P < 0.05）位点磷酸化均呈中度相关。我们的数据表明，在高血压早期，β-AR级联反应中的腺苷酸环化酶步骤未下调，训练增强的β-AR反应性可能在腺苷酸环化酶以外的水平介导。我们的数据还表明，与久坐的SHR心脏相比，训练后心脏在存在直接腺苷酸环化酶激动剂时β-AR的变力反应性得到改善。
