ABSTRACT
Gestational diabetes mellitus (GDM) affects 5-10% of pregnancies and increases the risk of fetal and maternal adverse outcomes. Interestingly, the vascular response to AngII is decreased by pregnancy while the response is increased by diabetes. It remains unclear how GDM affects vascular tone and how angiotensin II receptors contribute to these changes. In this work, we sought to establish the vascular impact of a hypercaloric diet-induced GDM through changes in AT1 and AT2 receptor's expression. Female rats fed for 7 weeks with standard (SD) or hypercaloric (HD) diet were divided at week 4. Half of the rats of each group were mated to become pregnant and those fed with a HD developed GDM. AngII-induced vasoconstriction was measured in thoracic or abdominal aorta rings using a conventional isolated organ bath and AT1 and AT2 receptors were searched by immunohistochemistry. Experiments where conducted on the pregnant standard diet group (PSD) and the pregnant hypercaloric-gestational diabetes mellitus group (PHD-GDM). Vasoconstriction was reduced in the thoracic aorta (P < 0.05 vs PSD) but increased in the abdominal aorta of PHD-GDM rats (P < 0.05 vs PSD). Blockade of AT2 receptors using PD123319 decreased vasoconstriction, particularly in the abdominal aorta of PHD-GDM animals (P < 0.05 vs PSD). PHD-GDM increased AT1 receptors expression (P < 0.05 vs PSD). Also, PHD-GDM reverted physiologic hypoglycemia and hypotension of healthy pregnancy. Findings provide new insight into the hypercaloric diet induced damage on the vasculature during pregnancy.
Subject(s)
Aorta, Abdominal/metabolism , Aorta, Thoracic/metabolism , Diabetes, Gestational/metabolism , Endothelium, Vascular/metabolism , Receptor, Angiotensin, Type 1/metabolism , Receptor, Angiotensin, Type 2/metabolism , Vasoconstriction , Angiotensin II/pharmacology , Angiotensin Receptor Antagonists/pharmacology , Animals , Aorta, Abdominal/drug effects , Aorta, Abdominal/physiopathology , Aorta, Thoracic/drug effects , Aorta, Thoracic/physiopathology , Diabetes, Gestational/physiopathology , Disease Models, Animal , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiopathology , Female , Pregnancy , Rats, Wistar , Receptor, Angiotensin, Type 1/agonists , Receptor, Angiotensin, Type 2/agonists , Signal Transduction , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacologyABSTRACT
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.
Subject(s)
Diabetes Mellitus, Experimental/physiopathology , Diabetes, Gestational/drug therapy , Diabetes, Gestational/physiopathology , Vasoconstriction/drug effects , Angiotensin II/administration & dosage , Animals , Diabetes Mellitus, Experimental/chemically induced , Diabetes, Gestational/chemically induced , Female , Humans , Losartan/administration & dosage , Phenylephrine/administration & dosage , Pregnancy , Rats , Vasoconstrictor Agents/administration & dosage , Vasodilation/drug effectsABSTRACT
Varios modelos experimentales reproducen las manifestaciones oculares de la diabetes mellitus, así es el caso del modelo no diabético de suplemento de sacarosa en la rata, el cual es un modelo no diabético que reproduce la nagiopatía diabética, con secreción de insulina normal. Durante seis meses de experimentación, encontramos cambios oculares importantes como cataratas bilaterales, despoblación de las células ganglionares de la retina, así como hipoagregabilidad plaquetaria in vitro. Todo esto, en ausencia de niveles altos de glucosa en la sangre, indica una alta disponibilidad metabólica de la glucosa, lo que determina las lesiones en el cristalino y retina encontradas en este estudio. Este modelo experimental tambien confirma el desarrollo de la hipoagregabilidad plaquetaria in vitro, la cual puede ser atribuída a la estimulación de las plaquetas in vivo.
