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Effect of age and COX‐2‐derived prostanoids on the progression of adult vascular dysfunction in the offspring of diabetic rats

Ramos‐Alves, FE ; de Queiroz, DB ; Santos‐Rocha, J ; Duarte, GP ; Xavier, FE

British journal of pharmacology, 2012-08, Vol.166 (7), p.2198-2208 [Periódico revisado por pares]

Oxford, UK: Blackwell Publishing Ltd

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Título:
Effect of age and COX‐2‐derived prostanoids on the progression of adult vascular dysfunction in the offspring of diabetic rats
Autor: Ramos‐Alves, FE ; de Queiroz, DB ; Santos‐Rocha, J ; Duarte, GP ; Xavier, FE
Assuntos: Acetylcholine - pharmacology ; Age Factors ; Animals ; Arterial hypertension. Arterial hypotension ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood Glucose - analysis ; Blood Pressure ; Cardiology. Vascular system ; cyclooxygenase ; Cyclooxygenase 1 - physiology ; Cyclooxygenase 2 - physiology ; Diabetes ; Diabetes Mellitus, Experimental - physiopathology ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; endothelial dysfunction ; Endothelium, Vascular - physiopathology ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Female ; fetal programming ; hypertension ; insulin resistance ; Male ; Medical research ; Medical sciences ; Membrane Proteins - antagonists & inhibitors ; Membrane Proteins - physiology ; Mesenteric Arteries - physiology ; Nitroprusside - pharmacology ; Pharmacology. Drug treatments ; Pregnancy ; Prostaglandins - physiology ; prostanoids ; Rats ; Rats, Wistar ; Research Papers ; Rodents
É parte de: British journal of pharmacology, 2012-08, Vol.166 (7), p.2198-2208
Notas: Both authors have contributed equally to this study.
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Descrição: BACKGROUND AND PURPOSE The present study was designed to determine how diabetes in pregnancy affects vascular function in their offspring, the influence of age and whether COX activation is involved in this effect. EXPERIMENTAL APPROACH Relaxation responses to ACh were analysed in mesenteric resistance arteries from the offspring of control rats (O‐CR) and those of diabetic rats (O‐DR) at 3, 6 and 12 months of age. TxB2, PGE2 and PGF2α release were determined by enzyme immunoassay. COX‐1 and COX‐2 expression were measured by Western blot analysis. KEY RESULTS O‐DR developed hypertension from 6 months of age compared with O‐CR. In O‐DR, relaxation responses to ACh were impaired in all ages studied and were restored by COX‐2 inhibition. TP receptor blockade (SQ29548) restored ACh relaxation in arteries from 3‐month‐old O‐DR while TP and EP receptor blockade (SQ29548 + AH6809) was required to restore it in 6‐month‐old O‐DR. In 12‐month‐old O‐DR, ACh relaxation was restored when TP, EP and FP receptors were blocked (SQ29548 + AH6809 + AL8810). ACh‐stimulated TxB2 was higher in all O‐DR. ACh‐stimulated PGE2 release was increased in arteries from 6‐ and 12‐month‐old O‐DR, whereas PGF2α was increased only in 12‐month‐old O‐DR. COX‐2, but not COX‐1, expression was higher in O‐DR than O‐CR. CONCLUSIONS AND IMPLICATIONS The results indicate an age‐dependent up‐regulation of COX‐2 coupled to an enhanced formation of vasoconstrictor prostanoids in resistance arteries from O‐DR. This effect plays a key role in the pathogenesis of endothelial dysfunction, which in turn could contribute to the progression of vascular dysfunction in these rats.
Editor: Oxford, UK: Blackwell Publishing Ltd
Idioma: Inglês

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Effect of age and COX‐2‐derived prostanoids on the progression of adult vascular dysfunction in the offspring of diabetic rats

Ramos‐Alves, FE ; de Queiroz, DB ; Santos‐Rocha, J ; Duarte, GP ; Xavier, FE

Oxford, UK: Blackwell Publishing Ltd

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