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

Gestational diabetes mellitus (GDM) decreases butyrylcholinesterase (BChE) activity and changes its relationship with lipids

Many conditions interfere with butyrylcholinesterase (BChE) activity, e.g., pregnancy or presence of the BCHE gene variant -116A can decrease activity whereas obesity and types I and II diabetes mellitus can increase activity. In this study, we examined BChE activity, -116A and 1615A BCHE gene variants, and anthropometric and biochemical variables associated with diabetes in patients with gestational diabetes mellitus (GDM) and in healthy pregnant women. BChE activity was measured spectrophotometrically using propionylthiocholine as substrate and genotyping of the -116 and 1615 sites of the BCHE gene was done with a TaqMan SNP genotyping assay. Three groups were studied: 150 patients with GDM, 295 healthy pregnant women and 156 non-pregnant healthy women. Mean BChE activity was significantly lower in healthy pregnant women than in women from the general population and was further reduced in GDM patients. BChE activity was significantly reduced in carriers of -116A in GDM patients and healthy pregnant women. Although GDM patients had a significantly higher mean body mass index (BMI) and triglycerides than healthy pregnant women, they had lower mean BChE activity, suggesting that the lowering effect of GDM on BChE activity was stronger than the characteristic enhancing effect of increased BMI and triglycerides

The effects of cadmium exposure on systolic blood pressure in rats.

<p>*P<0.05 vs matched exposure day of control group.^#P<0.05 vs first day of exposure of Cd-exposure group, determined using two-way ANOVA with Bonferroni’s post-test. The number of animals used is indicated in parentheses.</p

Sensitivity (pD2) and maximal responses (Emax) to phenylephrine, acetylcholine and sodium nitroprusside in aortic rings from cadmium-treated and control rats.

<p>The results are expressed as the mean ± SEM; Emax, maximal effect expressed as a percentage of the response induced by 75 mM KCl; pD2, -log one-half Emax. *P<0.05, Student’s t-test.</p

Phenylephrine concentration-response curves in the aortic rings of control and cadmium-exposed rats after SOD (A) or catalase (B) incubation.

<p>Densitometric analysis of the western blot to measure the superoxide dismutase Cu/Zn (Cu/ZnSOD) protein expression in the aortic rings of control and cadmium-treated rats (C). Representative blots are also shown. *P<0.05, Student’s t-test. The number of animals used is indicated in parentheses.</p

Densitometric analysis of western blot for eNOS protein expression (A) and NO production (B) in aortic rings incubated with DAF (2 mmol·L

<p>^−<b>1</b><b>).</b> Representative blots are also shown. *P<0.05, by Student’s t-test.</p

Phenylephrine concentration-response curves in the aortic rings of control (A) and cadmium-exposed (B) rats after apocynin incubation.

<p>Differences in the area under the concentration-response curve (dAUC) in the aortic rings of control and cadmium-treated rats after apocynin incubation (C). Densitometric analysis of the western blot to measure the gp^91phox protein expression in aortic rings (D). Representative blots are also shown. *P<0.05, Student’s t-test. The number of animals used is indicated in parentheses.</p

Phenylephrine concentration-response curves after endothelium removal (A, B) or N-nitro-L-arginine methyl ester incubation (L-NAME, 100 µM) (D, E) in the aortic rings of control and cadmium-exposed rats.

<p>E-: endothelium-denuded, E+: intact segments. Differences in the area under the concentration-response curves (dAUC) in endothelium–denuded and intact segments (C) and in the presence and absence of L-NAME (F). * and+P<0.05, Student’s t-test. The number of animals used is indicated in parentheses.</p

The effects of endothelium removal (E⁻), L-NAME, losartan, enalapril, SOD, catalase and apocynin on the sensitivity (pD2) and maximal response (Emax) to phenylephrine in aortic rings from cadmium-treated and control rats.

<p>The results are expressed as the mean ± SEM; Emax, maximal effect expressed as a percentage of the response induced by 75 mM KCl; pD2, -log one-half Emax. E- endothelium removal, E+ intact endothelium, SOD, superoxide dismutase. P<0.05 <i>vs</i> control rats (^#) and cadmium-treated rats (*), determined using Student’s t-test.</p

The effects of cadmium exposure on concentration-response curves to phenylephrine (A), acetylcholine (B) and sodium nitroprusside (C).

<p>*P<0.05, Student’s t-test. The number of animals used is indicated in parentheses.</p