Abstract
Diabetic conditions increase vascular reactivity to angiotensin II in several studies but there are scarce reports on cardiovascular effects of hypercaloric diet (HD) induced gestational diabetes mellitus (GDM), so the objective of this work was to determine the effects of HD induced GDM on vascular responses. Angiotensin II as well as phenylephrine induced vascular contraction was tested in isolated aorta rings with and without endothelium from rats fed for 7 weeks (4 before and 3 weeks during pregnancy) with standard (SD) or hypercaloric (HD) diet. Also, protein expression of AT1R, AT2R, COX-1, COX-2, NOS-1, and NOS-3 and plasma glucose, insulin, and angiotensin II levels were measured. GDM impaired vasoconstrictor response (P < 0.05 versus SD) in intact (e+) but not in endothelium-free (e−) vessels. Losartan reduced GDM but not SD e− vasoconstriction (P < 0.01 versus SD). AT1R, AT2R, and COX-1 and COX-2 protein expression were significantly increased in GDM vessels (P < 0.05 versus SD). Results suggest an increased participation of endothelium vasodilator mediators, probably prostaglandins, as well as of AT2 vasodilator receptors as a compensatory mechanism for vasoconstrictor changes generated by experimental GDM. Considering the short term of rat pregnancy findings can reflect early stage GDM adaptations.
Highlights
7% of all pregnancies are complicated by gestational diabetes mellitus (GDM), a health problem that has recently been propelled by climbing obesity rates [1]
We developed an hypercaloric diet based model of GDM that alter glucose tolerance test (GTT) in pregnant rats without changing basal blood glucose levels, resembling the features of human obesity associated GDM
Insulin (1.96 ± 0.2 ng/mL versus 1.23 ± 0.08 ng/mL, P < 0.05, hypercaloric diet (HD) versus SD, resp.) and angiotensin II (119.9 ± 5.36 ng/mL versus 101.9 ± 6.62 ng/mL, P < 0.05, HD versus SD, resp.) concentrations were significantly increased in HD pregnant rats (Figure 1), as well as HOMA index (10.70 ± 1.05 versus 7.40 ± 0.79, HD versus SD, resp.) (Figure 1(c))
Summary
7% of all pregnancies are complicated by gestational diabetes mellitus (GDM), a health problem that has recently been propelled by climbing obesity rates [1]. Women with GDM are at increased risk for the development of complications such as macrosomic product, preeclampsia [4], and diabetes, usually type 2, after pregnancy [5]. Both obesity and overweight are conditions associated with a decreased insulin sensitivity [6] and have been identified as the main risk factors for GDM [7]. In this sense, insulin resistance (IR) is known to be a key factor for vascular complications such as endothelial dysfunction and impaired vascular relaxation
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