Post-Weaning Protein Malnutrition Increases Blood Pressure and Induces Endothelial Dysfunctions in Rats

Malnutrition during critical periods in early life may increase the subsequent risk of hypertension and metabolic diseases in adulthood, but the underlying mechanisms are still unclear. We aimed to evaluate the effects of post-weaning protein malnutrition on blood pressure and vascular reactivity in aortic rings (conductance artery) and isolated-perfused tail arteries (resistance artery) from control (fed with Labina®) and post-weaning protein malnutrition rats (offspring that received a diet with low protein content for three months). Systolic and diastolic blood pressure and heart rate increased in the post-weaning protein malnutrition rats. In the aortic rings, reactivity to phenylephrine (10−10–3.10−4 M) was similar in both groups. Endothelium removal or L-NAME (10−4 M) incubation increased the response to phenylephrine, but the L-NAME effect was greater in the aortic rings from the post-weaning protein malnutrition rats. The protein expression of the endothelial nitric oxide isoform increased in the aortic rings from the post-weaning protein malnutrition rats. Incubation with apocynin (0.3 mM) reduced the response to phenylephrine in both groups, but this effect was higher in the post-weaning protein malnutrition rats, suggesting an increase of superoxide anion release. In the tail artery of the post-weaning protein malnutrition rats, the vascular reactivity to phenylephrine (0.001–300 µg) and the relaxation to acetylcholine (10−10–10−3 M) were increased. Post-weaning protein malnutrition increases blood pressure and induces vascular dysfunction. Although the vascular reactivity in the aortic rings did not change, an increase in superoxide anion and nitric oxide was observed in the post-weaning protein malnutrition rats. However, in the resistance arteries, the increased vascular reactivity may be a potential mechanism underlying the increased blood pressure observed in this model

Composition (g/g %) of the Regional Basic Diet (RBD) and the control diet.

1<p>According to the Laboratory of Experimentation and Analysis of Food (LEEAL), Nutrition Department, Federal University of Pernambuco.</p>2<p>As indicated by the manufacturer (Purina Agriband, Paulínia, SP, Brazil).</p

Body weight (g) measurements of control (CT) and post-weaning protein malnutrition (Malnutrition) offspring.

<p>Values are expressed as the mean ± SEM.</p>*<p><i>P</i><0.05 Control <i>vs.</i> Malnutrition, Student's <i>t-</i>test.</p

Densitometric analysis of the Western blots for endothelial NO synthase (eNOS) protein expression in the isolated aortic rings from Wistar rats (CT, N = 9) and post-weaning protein malnutrition (Malnutrition, N = 9).

<p>The number of preparations is indicated in parenthesis. Each bar represents means ± S.E.M as the ratio between the signal for the eNOS protein and the signal for α-actin. * <i>P<0.05</i> for CT <i>vs.</i> Malnutrition by Student's <i>t</i>-test. Representative blots are shown.</p

(A) Changes in the mean perfusion pressure (MPP) produced by phenylephrine (PHE) in tail vascular beds from the control (CT) and post-weaning protein malnutrition groups (Malnutrition).

<p>(B) Concentration-response curves produced by acetylcholine (ACh) in the tail vascular beds previously contracted with potassium chloride (KCl, 65 mM) (C) Concentration-response curves produced by sodium nitroprusside (SNP) in the tail artery bed previously contracted with with potassium chloride (KCl, 65 mM). The number of preparations is indicated in parenthesis. The results are expressed as the means ± SEM. * <i>P</i><0.05 for Rmax: CT <i>vs.</i> Malnutrition, Student's <i>t-</i>test.</p

Systolic (SBP, mmHg) and diastolic (DBP, mmHg) blood pressure and heart rate (HR, bpm) determination in the control (CT) and post-weaning protein malnutrition (Malnutrition) adult rats.

<p>Values are expressed as the means ± SEM.</p>*<p><i>P</i><0.05 Control <i>vs.</i> Malnutrition, Student <i>t</i>-test.</p