Background: 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.
Methods And Results: 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.
Conclusion: BRD triggers sympathetic exacerbation and dysfunction in Ca handling, accompanied by early onset of hypertension and left ventricle congestive heart failure.
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