Mendes Luiza V P, Gonsalez Sabrina R, Oliveira-Pinto Leonardo M, Pereira-Acácio Amaury, Takiya Christina M, Nascimento José H M, Einicker-Lamas Marcelo, Vieyra Adalberto, Cunha Valéria M N, Lara Lucienne S
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Int J Cardiol. 2017 Jul 1;238:43-56. doi: 10.1016/j.ijcard.2017.03.110. Epub 2017 Mar 27.
We investigated whether a chronic low-protein multideficient diet (BRD) from weaning turns on cardiovascular adaptive responses that could culminate in hypertension and heart failure.
Systolic pressure (SP) and heart rate (HR) were determined in CTRL (normal diet) and BRD rats. Plasma albumin, plasma urea and urinary urea excretion decreased in BRD rats. In this group, echocardiography and the Langendorff technique showed: (i) increased HR and hypertension; (ii) decreased LVDP, dP/dt, dP/dt, cardiac output, ejection fraction, stroke volume and left ventricular diameter. BRD rats were less sensitive to isoproterenol (ISO) in LVDP and dP/dt, with unchanged dP/dt; Pressure-volume relationships indicated left-oriented shifts in LVDP, SP and DP, and decreased capacitance compared to CTRL. BRD rats had higher cardiac and lung indexes, accompanied by muscle atrophy and recent ventricular-infarcted areas, higher ventricular β1-AR content, and decreased β2-AR and α1-AR. Propranolol treatment gave similar ISO responses in both groups, disappearance of the infarcted regions and, except for β2-AR, recovery of normal receptor expression. BRD rats had intense stimulation of plasma membrane Ca-ATPase (PMCA) activity, with increased Ca affinity and inhibition of the sarco(endo)plasmic reticulum Ca-ATPase (SERCA). Ventricular phospholamban increased and Na/Ca exchanger decreased. PMCA activity correlated with an increase in its PKC-mediated phosphorylation, overlying a decrease in PKA-catalyzed phosphorylation. Propranolol normalized PKC and PKA activities with recovery of PMCA but not SERCA.
BRD triggers sympathetic exacerbation and dysfunction in Ca handling, accompanied by early onset of hypertension and left ventricle congestive heart failure.
我们研究了从断奶开始的慢性低蛋白多营养素缺乏饮食（BRD）是否会引发心血管适应性反应，最终导致高血压和心力衰竭。
测定了对照组（正常饮食）和BRD大鼠的收缩压（SP）和心率（HR）。BRD大鼠的血浆白蛋白、血浆尿素和尿尿素排泄量降低。在该组中，超声心动图和Langendorff技术显示：（i）心率增加和高血压；（ii）左心室舒张末期压力（LVDP）、dp/dt、dP/dt、心输出量、射血分数、每搏输出量和左心室直径降低。BRD大鼠在LVDP和dp/dt方面对异丙肾上腺素（ISO）的敏感性较低，dP/dt不变；压力-容积关系表明，与对照组相比，LVDP、SP和DP向左偏移，电容降低。BRD大鼠的心脏和肺指数较高，伴有肌肉萎缩和近期心室梗死区域，心室β1-肾上腺素能受体（β1-AR）含量较高，β2-AR和α1-AR降低。普萘洛尔治疗使两组的ISO反应相似，梗死区域消失，除β2-AR外，正常受体表达恢复。BRD大鼠的质膜钙ATP酶（PMCA）活性受到强烈刺激，钙亲和力增加，肌浆网钙ATP酶（SERCA）受到抑制。心室受磷蛋白增加，钠/钙交换器减少。PMCA活性与其PKC介导的磷酸化增加相关，同时PKA催化的磷酸化减少。普萘洛尔使PKC和PKA活性恢复正常，PMCA恢复但SERCA未恢复。
BRD引发交感神经亢进和钙处理功能障碍，伴有高血压和左心室充血性心力衰竭的早期发作。
